Plasma level of quinidine in Myanmar patients with falciparum malaria

Plasma level of quinidine on 14 adult male falciparum malaria patients were studied. The patients consisted of 7 with low level of parasites in blood and 7 with high level of parasites ( > 5 percent RBC parasitised). All the patients received infusion of quinidine 15 mg/kg body weight diluted in 500 cc normal saline as initial loading dose, followed by infusion 7.5 mg/kg body weight 8 hourly for another two doses and than followed by oral quinidine 7.5 mg/kg 3 times a day for 7 days. Plasma for quinidine estimation was collected at the following hours: 0,1,2,4,6,9,12,36,48 hours and on days. 3,4 and 7 of the study period. In patients with low level of parasites, the maximum plasma quinidine level reached the peak 6.8 ug/ml onthe 4th day of treatment. After the first dose of treatment, it reached 4.3 ug/ml at 2nd hour. Among patients with high level of parasites, the maximum plasma quinidine concentration was 6.6 ug/ml and this concentration was obtained at 9th hour after the first dose. The mean plasma concentration of the 2 groups was not statistically different.

The effect of intramuscular loading dose of quinine on Myanmar patients (children and adults) with falciparum malaria

The effect of three doses of intramuscular quinine followed by oral quinine on ten adults and ten children with falciparum malaria (half of each group were highly parasitised) were studied. There were no complications associated with this method of therapy. the level of serum quinine in all the adults reached above the minimal inhibitory concentration (MIC) from the 2nd hour of the drug administration. So this method of administration should be recommended for severely ill patients before referral to hospitals. Anong the children, eight responded well to the therapy and the serum quinine level rose above MIC level from the second hour as in adults. There were two patients who failed to respone to the treatment. One had persistantly high level of quinine and was misdiagnosed as a case of cerebral malaria instead of quinine toxicity. He responded well when quinine was omitted and replaced with mefloquine. Another child had persistantly low level of quinine. He developed cerebral sings and symptoms and also responded well to mefloquine. Thus it is suggested that the level of serum quinine should be monitroed in children if possible, or toxicity ot quinine should be watched.

The effect of quinine and Quinidine on patients with highly parasitised falciparum malaria ( A double blind study )

Sixty patients with high level of parasites in the blood (i.e., more than 2

of RBCs parasitised)were chosen for the study. They were paired in sex and associated complications as nearly as possible. The first group of patients was treated with drug (A) and the remaining with drug (B). Drugs (A) and drug (B) consisted fo quinine or quinidine, (injection and tablets) which is unknown to investigators. 15 mg/ kg quinine or quinidine was given as a loading dose infused over 4 hours followed by 2 doses of 7.5mg/kg base also infused over 4 hours each at 8 hours intervals. This was followed by oral therapy. The oral drugs were continued as 7.5 mg/ kg base 3 times/ day till day 7. the efficacy of the 2 drugs were compared in terms of mortality, development of complications parasite and fever clearance, time. All patients survived, significantly higher level of serum quinine was recorded, when compared to quinidine through out the study.Serum insulin of five pairs of patients and blood glucose level of 15 pairs of patients were within the normal range (in all patients) throughout the study period. Blood glucose level in patients treated with quinine is significantly lower than those treated with quinidine at the first 36 hours of treatment. Since the parasite clearance time, fever clearance time mortality rate and recrudescence rate between the 2 groups of patients were comparable, we conclude that quinidine is clinically equal but not more potent than quinine. It is probably more toxic because of more ECG changes. Quinidine may be used as alternative only if quinine is not available.

The importance of frequent PCV monitoring and timely fresh blood transfusion in the management of severe falciparum malaria (Short report)

In our experience , cerebral malaria is not the only cause of death among patients with malaria. Low pack cell volume (PCV) was often associated with the time of death of patients. During 1987 we had a patient with PCV 31

and while preparing for the treatment, his PCV fell to 18

in two hours and he expired. We also had four patients with PCV 12

, 18

, 16

and 15

at time of admission to hospital. Hence we started following PCV of the patients with complicated malaria and fresh blood transfusion was given to all those with PCV less then 20

. This is the report of the first ten cases treated with method.

Clinical significance of fibrinogen/fibrin degradation products (FDP) in falciparum malaria

The relationship between the levels of FDP in the serum, parasite count and the severity of the clinical manifestations were studied in 89 patients with falcoparum malaria. Serum FDP levels were found to be related to the level of asexual parasite count as well as to the severity of the clinical manifestations of falciparum malaria. It is thus suggested that the measurement of serum FDP can be used to identify hihg risk group of falciparum malaria cases.

Electrocardiographic effect of quinine and quinidine in the treatment of falciparum malaria

Quinidine has been suggested as an acceptable alternative to quinidine in the treatment of falciparummalaria. To compare the electrocardiographic effects of quinine and quinidine in falcaparum malaria, sixty patients with more than 2 per cent of parasitized red cells were chosenand paired as closely as possible. The study was double-blind. 15 mg/kg quinine or quinidine was given as a loading dose infused over 4 hours followed by 2 doses of 7.5 mg/kg base at 8 hourly intervals. Oral quinine or quinidine as 7.5 mg/kg base 3 times/day was then continued till day 7. Satisifactory 12 lead electrocardiograms were obtained from 58 patients on day 0, after 24 hours, on day 3 and on day 7. Overall there was no significant change in PR interval or ORS duration. The pretreatment QTc was 443+ or -30 msec in the quinine group (n=30) and 438+ or -25 msec in the quinidine group (n=28) with no significant difference. MAximum QTc prolongation occured on the third day in both groups being 481+ or -28msec in the quinine group and this was significantly less than 532+ or -55 msec seen in the quinidine group. QTc > 550 msec was found in 46.6 per cent in the quinidine group but in only one in the quinine group.T wave flattening occurred in 62 per cent in the quinidine group but in only 25 per cent in the quinine group. No dysrhythmias were recorded in this study but because of the excessive prolongation of the Qtc caused by quinidine, we conclude that we should be cautious about the use of quinidine for falciparum malaria.

Disposition kinetics of intramuscular quinine in Myanmar adult patients with falciparum malaria

Intramuscular quinine pharmacokinetic study was made on ten Myanmar adults who attended Thayarwady Civil Hospital for the treatment of Falciparum malaria. The patients were given intramuscular quinine dihydrochloride (15 mg base/kg) body weight following by another two doses of intramuscular quinine 7.5 mg per kg and oral quinine sulphate 7.5 mg three times daily till day-7. Plasma conscentrations of quinine at various post-drug time intervals were assayed by the benzene extraction fluorescence (EF) method (1). Plasma quinine concentrations until 6 hours after the laoding dose were analysed for pharmacokinetic parameters. The level of quinine reached the minimum inhibitory concentration level within the first 1-2 hours of starting treatment. The drug was found to ge well tolerated by the patients with absence of tissue necrosis at the site of injection.

Lepromin reaction in patients with falciparum malaria

The study was done to find out if ther is any relation between leprosy and malaria, and to find out the cellular responses of the host to Mycobaterium leprae extract in malaria patients. As a preliminary step lepromin was tested on malaria patients.57.7 per cent of malaria patients were lepromin negative or doubtful reaction. Among the controls only 7 per cent showed negative or doubtful reaction.

Diagnosis of resistant strains of Plasmodium Falciparum after chloroquine and amodiaquine therapy from 42 to 72 hours of drug administration

The effect of chloroquine and amodiaquine on the in vivo development of asexual parasites (trophozoide from) during the treatment of falciparum malaria was studied on 48 patients. They consisted of 6 patients who were sensitive, 8 patients with R1 and 6 patients with R11 resistence to chloroquine, and 5 patients who were sensitive, 13 patients with R1 and 10 patients with R11 resistance to amodiaquine. Percentage distribution of tiny, small and large forms of trophozoites were counted every 6 hours till blood smears were negative. From the results we may be able to predict the presence of resistant strains of parasite between 48-72 hours of treatment.

The Response of Children with Falciparum Malaria to Quinine

10 children with falciparum malaria (highly parasitised) who had not had previous antimalarial therapy were chosen for the study-Quinine dihydrochloride 10 mg/kg body weight diluted in 150-200ml of normal saline was administered as infusion over 4-5 hours as the first dose. Subsequent doses were given orally as quinine sulphate 10 mg/kg body weight 8 hourly. The total duration of treatment was 7 days. The serum quinine levels, the parasite count, and the clinicalprogress were determined at different intervals of treat,emt/ 9 pit pf 10 cjo;drem jad serim quinine levels above Burmese MIC level of 4.3 mg per litre and no signs and symptoms of quinine toxicity was observed even in patients with high serum quinine levels. (ie.> 10 u gm/ml.)

Drug Resistance in Falciparum Patients Treated with Mefloquine-sulphadoxine-pyrimethanine in Myanmar

3 out of 32 P. falciparum malaria patients treated with Mefloquine-Sulfadoxig-Pyrimethamine combinations at Tharrawaddy Township Hospital, Myanmar failed to respond to the drug. One of the patients was regarded as R2 and another two as R1 resistance to the drug. One of them was also resistance to Mefloquine and Quinine in in-vitro studies. We conclude that there are patients who failed to respond to Mefloquine-Sulfadoine-Pyrime-thamine even in areas where Mefloquine had never been used.

Study of the effect of single dose primaquine on gametocytaemia and infectivity among Amodiaquine-treated P.falciparum malaria patients

One hundred and five patients who attended Thayarwady Civil Hospital during 1987 and 1988 malaria seasons were studied. They were divided into three groups. Among 35 patients who were treated with amodiaquine alone, 23-33 per cent of the patients showed gametocytes in blood during days 14, 21 and 28 of therapy. Among those patients with gametocytes in blood, 50 to 63 percent of patients showed that they were viable by exflagellation method. Follow-up of one patient showed viable gametocytes in blood till 51st day of drug therapy. Among 45 patients treated with amodiaquine and primaquine (45 mg single dose given on day 3), 31 per cent of patients showed gametocytes on day 7, later only 0-10 per cent of patients showed gametocytes on day between 14, 21 and 28. Among the till day 4. From day 5 they were not viable. Except one patient who showed gametocytes at day 28 was proved to be R11 resistant to amodiaquine. Among 25 patients treated with amodiaquine and primaquine (45 mg single dose: given on day 1 of hospital admission ) 36 per cent showed gametocytes on day 7 and 42 per cent showed gametocytes on day 28. Of these 26 per cent patients with gametocytes which appeared on day 28 was proved to be viable. It is suggested that primaquine 45 mg is effective to control infectivity of gametocytes in blood. It is also suggested that primaquine should be given on 3rd day of hospital admission to get the most beneficial effect.

Disposition kinetics of infusion quinine in (Adult) Myanmar falciparum malaria patients

To study the pharmacokinetics of infusion quinine in Myanmar patients, 14 adults with falciparum malaria (half of them were highly parasitised i.e more than 5

of rbc parasitised with malaria parasites) were infused with Quinine dihydrochloried 15 mg/kg body weight initially, followed by 7.5 mg/kg 8 hourly for 2 doses. This was followed by oral administration of Quinine sulphate 7.5 mg/kg for 7 days. Plasma concentrations of quinine until 6 hours after the initial loading dose were analysed for pharmacokinetic parameters.

Hospital based in vivo monitoring of the degree of resistance of P.Falciparum to standard anti-malarials

This preliminary study was done to monitor the changing trend in sensitivity of anti-malarials at a fixed hospital in central Burma near Pegu Mountain Range. During 1986 malarial season out of 15 patients treated with chloroquine (6.6per cent) was resistant at R2 level and (73.3 per cent) were resistant at R1 level. Remaining 20 per cent of patients were either S (sensitive)of R1 (resistant). Out of 29 patients treated with amodiaquine (6.9 per cent) were resistant at R2 level and (51.7 per cent) were resistant at R1 level. (13.8 per cent) patients were proved as sensitive and the remaining (27.6 per cent) patients were either S (sensitive) or R1 (resistant). Out of 24 patients treated with sulphadoxine pyrimethamine (16.7 per cent) were resistant at R2 level. 50 per cent were resistant at R1 level. (20.8 per cent) cases were sensitive to the drug. The remaining 12.5 per cent of patients were either S (sensitive) or R1 (resistant). Out of 31 patients treated with quinine (6.5 per cent) were resistant at R2 llevel. (9.7 per cent) were resistant at R1 level. (48.3 per cent) were sensitive to the drug. Remaining (35 per cent) were either S (sensitive) or resistant at R1 level. Out of 35 patients treated with mefloquine sulphadoxine pyrimethamine (3.0 per cent) was resistant at R2 level. (12.1 per cent) were resistant at R1 level. (69.6 per cent) were sensitive to the drug and the remaining (15.2 per cent) of patients were either S or R1 resistant. The problems faced with the present method of drug monitoring will be discussed. Although re-infection during the follow up period could not be totally excluded it may be concluded that significant resistance to quinine exists and mefloquine resistance may also become a problem in the not too distant future.

Clinical presentation of H.I.V positive intravenous drug abusers

Of 45 persons who were tested for the presence of HIV antibodies at Wards 1 & 2 , Yangon General Hospital from April 1989 to November 1989, all 26 HIV positive cases were male intravenous drug abusers (ELISA and Western blot tests positive). Mean age was 29.4 years . Pulmonary tuberculosis was the commonest presentation with 6 cases followed by infective endocarditis in 4 cases and seroconversion illness in 4. Other clinical presentations included septicaemia (3), viral hepatitis (2), drug overdose (3), malaria (3) and pneumonitis (1). Overall mortality was high nearly 40 per cent even though none of the cases had features of AIDS as defined by CDS/WHO.