Causes, magnitude and management of burns in under-fives in district hospitals in Dar es Salaam, Tanzania.

OBJECTIVES: To determine the causes, magnitude and management of burns in children under five years of age who were admitted in the district hospitals of Dar es Salaam City, Tanzania. METHODS: In this study, a total of 204 under fives were enrolled. Questionnaires were used to elicit if the parent/caretaker had the knowledge of the cause of the burns, what was done immediately after burn injury, first aid given immediately after burn, source of the knowledge of first aid and when the child was taken to the hospital. Also the questionnaire was cited with data on the management of burns in the hospitals through observation and checking the treatment files. RESULTS: Forty nine percent were males while 50.5% were females. Most of the children (54.9%) were aged between 1-2 years. 78.4% had scalds while 21.6% had flame burns. No children were found to have burns caused by chemicals or electricity. Most of the burns (97.5%) occurred accidentally, although some (2.5%) were intentional. 68.6% of these burn injuries occurred in the kitchen. Immediately after burn 87.3% of the children had first aid applied on their wounds while 12.7% didn't apply anything. Of the agents used, honey was the most used (32.8%) followed by cold water (16.7%). The source of knowledge on these agents was from relatives and friends (72.5%), schools (7%), media (6%) and medical personnel (14%). The study further revealed that analgesics, intravenous fluids, antiseptics and antibiotics were the drugs used for treatment of burns in the hospital and that there was no specialized unit for burns in the hospitals. CONCLUSIONS: Causes of childhood burns are largely preventable requiring active social/medical education and public enlighten campaigns on the various methods of prevention. The government to see to it that hospitals have specialized units for managing burn cases and also the socio-economic status of its people be improved.

Self-medication with chloroquine in a rural district of Tanzania: a therapeutic challenge for any future malaria treatment policy change in the country.

BACKGROUND: Malaria continues to be a leading cause of morbidity and mortality in children aged 5 years or younger in Tanzania. Children who develop mild disease can rapidly progress to severe malaria (cerebral malaria with convulsions) and even death, because of mismanagement, delays and inappropriate drug therapy in the remote areas where primary health care facilities are inaccessible or unavailable. The threat is particularly severe in those who are unable to take oral medications. OBJECTIVE: To identify treatment strategies adopted by mothers or guardians of children under five for malaria. METHOD: A cross-sectional descriptive study using a questionnaire and blood sampling was carried in Kibaha district primary health care facilities. Over 500 mothers/guardians of sick children aged up to 5 years who visited the public facilities seeking care were interviewed in order to assess what management they offered to their sick children in their homes prior to coming to the public health facilities. RESULTS: Seventy-four per cent of the mothers/guardians stated that they had given some medication to their children prior to visiting the public health facilities: mostly analgesics (asprin, paracetamol) and chloroquine. Eighty-five per cent of the sick children given chloroquine had whole blood chloroquine levels above 500 nmol/L and 33% of the sick children with whole blood chloroquine levels above 1,000 nmol/L had malaria parasites in their blood. Of the sick children given chloroquine at the health facilities, 63% had no malaria parasites in their blood. CONCLUSION: There is a need to educate both rural communities, and health care providers about rational prescribing, dispensing and use of antimalarials.

Comparative bioavailability of oral sugar-coated and plain formulation of chloroquine phosphate marketed in Tanzania.

The bioavailability of chloroquine from a single oral dose (10 mg/kg body weight) of a sugar-coated (Dawaquin) and a plain formulation (Shellyquine) of chloroquine phosphate were compared in two groups of 10 volunteers each, following an overnight fast. Whole blood chloroquine concentrations were measured using high-performance liquid chromatography (HPLC) and bioavailability was determined by measuring area under the blood chloroquine concentration curve (AUC ng mL(-1) h) and the peak blood chloroquine concentration (Cpmax ng/mL). The AUC and Cpmax for Shellyquine were 4396.3 +/- 833 ng mL(-1) h and 162 +/- 14 ng/mL, respectively. The AUC and Cpmax for Dawaquin were 2060 +/- 339 ng mL(-1) h and 56.6 +/- 5.2 ng/mL, respectively. Shellyquine was significantly more bioavailable than Dawaquin (P<0.001). Although the Cpmax for Dawaquin was higher than the required therapeutic level for sensitive Plasmodium falciparum of 30 ng/mL, its blood levels may not guarantee a rapid clearance of parasites. The differences between the two formulations point to a problem in the quality of pharmaceuticals marketed in this country, whose extent need to be ascertained further. Failure of chloroquine phosphate in this country has already been declared by the Ministry of Health, and the potential contribution of poorly formulated products remains a subject of debate.

The effect of Phyllanthus amarus aqueous extract on blood glucose in non-insulin dependent diabetic patients.

The glycaemic response to 124.5 +/- 9.3 (mean +/- SD) g of pancakes was monitored in 21 non-insulin dependent diabetic (NIDDM) patients while on oral hypoglycaemics, after a 1-week washout period and after a 1-week twice daily treatment with 100 mL of an aqueous extract from 12.5 g of powdered aerial parts of Phyllanthus amarus. After the 1-week washout period, the fasting blood glucose (FBG) and postprandial blood glucose increased significantly compared with treatment on oral hypoglycaemics ( p < 0.05). After a 1-week herbal treatment no hypoglycaemic activity was observed. Both FBG and postprandial blood glucose remained very similar to that recorded after the washout period ( p > 0.05). Both liver and renal functions based on alanine transaminase (ALAT) and serum creatinine, respectively, were not significantly affected by the use of the extract. Although the lymphocyte and monocyte levels were significantly decreased ( p < 0.05) and the granulocyte level was significantly increased after treatment ( p < 0.05) the overall total white blood cell (WBC) count and haemoglobin (Hb) were not significantly affected by the 1 week herbal treatment. We conclude that 1 week treatment with the aqueous extract of Phyllanthus amarus was incapable of lowering both FBG and postprandial blood glucose in untreated NIDDM patients.

Comparative in vitro and in vivo study of a sugar-coated chloroquine preparation marketed in Tanzania versus an ordinary brand.

OBJECTIVE: To investigate the absorption and the quality of a sugar-coated chloroquine (CQ) marketed in Tanzania. METHOD: Twenty healthy volunteers were randomised to take either the test brand (group A) or a control chloroquine phosphate (group B). Each subject received 300 mg chloroquine base. Whole blood dried on filter papers were collected at time 0 and at 15 and 30 min and at 1, 2, 3, 4, 6, 8, 24, 36, 48, 72 and 168 h after drug intake. Urine samples were collected at time 0, 0-4 h, 4-8 h, 8-24 h, 24-48 h and 48-72 h after drug administration. In an in vitro study, six tablets from each of the two CQ preparations were checked for the amount of active drug contained in each tablet and their dissolution rates. RESULTS: The blood concentration Area Under the Curve (AUC) of group B was about 10% larger than that of group A. The total amounts of CQ plus deethylchloroquine excreted with the urine during the 72-h study period were 5% for group A and 6% for group B. None of the pharmacokinetic parameters were significantly different between the two groups. All the tablets contained the labelled amount of chloroquine; however, one tablet from the test drug failed to fulfil the required dissolution rate. CONCLUSION: We found no major difference between the AUCs of the two CQ preparations, but the sugar-coated brand has shown to have variable dissolution rate.

Prescribing habits in church-owned primary health care facilities in Dar Es Salaam and other Tanzanian coast regions.

OBJECTIVE: To assess prescribing practice of Primary Health Care (PHC) workers in church owned health care facilities using WHO drug use indicators. DESIGN: A cross-sectional study in which twenty primary health care facilities were randomly selected. Prescribing indicators were obtained by analysing outpatient records retrospectively for the past 14 months between January 1997 and February 1998. This period was chosen because of compete records of outpatient attendances. Patient care and facility indicators were recorded prospectively during the study period. SETTING: The study was conducted in the Coast and Dar es Salaam regions of Tanzania. Six districts were randomly selected from both regions. The selected districts included Ilala, Temeke and Kinondoni in Dar es Salaam, Kibiti, Bagamoyo and Kisarawe in Coast region. SUBJECTS/MATERIALS: Twenty primary health care facilities were randomly selected from the chosen districts. Patient registers were collected and patients' characteristics including age, sex, diagnosis, and drugs prescribed for the period January 1997 to February 1998 were recorded on data collection forms. Patient care indicators were measured by recording consultation time, dispensing time, per cent of drugs actually dispensed and adequately labelled whereas patients' knowledge of correct drug dosage was obtained using exit interviews. Verification of facility indicators was done by direct observation. RESULTS: The average number of drugs per prescription was 2.3 (range 1.8-2.8). Generic prescribing prevailed with a mean of 75.5% of all drugs. Antibiotic and injection encounters per prescription was 35.4 and 19%, respectively. Most drugs were prescribed according to the essential drug list of Tanzania (NEDLIT). Patient's average consultation time was 3.6 minutes whereas average dispensing time was 39.9 seconds. On average, 87% of all drugs dispensed were adequately labelled and patients' knowledge of correct dose was adequate. All facilities possessed drugs for treating important illnesses, all had reference educational materials. CONCLUSION: The study shows that there is an overuse of injections 19% +/- 1.7 (range 0.73%) compared to the recommended figure of 15%. The use of antibiotics appears appropriate when compared with the morbidity patterns in the study areas. A focus group discussion with prescribers in these facilities to address the question of overuse of injections is needed in order to plan an appropriate intervention.

Slow chloroguanide metabolism in Tanzanians compared with white subjects and Asian subjects confirms a decreased CYP2C19 activity in relation to genotype.

BACKGROUND: We have previously found decreased CYP2C19 activity in Tanzanians tested with mephenytoin and omeprazole in relation to genotype when compared with white and Asian subjects. OBJECTIVE: We investigated the impact of CYP2C19 genotype and phenotype on chloroguanide (INN, proguanil) metabolism to its metabolites cycloguanil and 4-chlorophenylbiguanide. METHODS: A single oral chloroguanide dose was given to 25 healthy Tanzanian subjects with CYP2C19 genotypes (CYP2C19*1, CYP2C19*2, and CYP2C19*3). Homozygous wild-type and mutated genotype groups were chosen randomly, but the heterozygous genotype group was chosen with a range in phenotype. We used a novel HPLC method for drug determination. RESULTS: Pharmacokinetics of chloroguanide did not differ between groups. Maximum plasma concentration (Cmax) and area under the plasma concentration versus time [AUC(0-infinity)] for cycloguanil was significantly lower (t test P < .05) in the homozygously mutated group compared with the homozygously wild-type group. There were similar significant group differences of median urinary excretion. The chloroguanide/cycloguanil ratio closely correlated (r(s) = .87) with omeprazole metabolic ratio, confirming that Tanzanian subjects are generally slower CYP2C19 metabolizers. It also confirms that CYP2C19 genotype and phenotype predicts cycloguanil formation. In addition, a 3-hour plasma sample metabolic ratio also seems to be a proper time for omeprazole phenotyping in Tanzanian subjects. Because the plasma concentrations of cycloguanil and 4-chlorophenylbiguanide covary (r(s) = .89), it is now suggested that their formation be catalyzed by the same enzyme (ie, CYP2C19) through a common intermediate, the structure of which is also presented. CONCLUSIONS: As shown in an earlier study, also with a third substrate, Tanzanians have a lower capacity to form cycloguanil than white and Asian subjects. Individuals with two mutated alleles have lower metabolic capacity than individuals with two wild-type alleles or individuals in the heterozygous group, which may lead to chloroguanide therapeutic failure. This knowledge should be important when selecting appropriate patients and doses of chloroguanide in different populations.

Chloroquine blood concentrations and malaria prophylaxis in Tanzanian women during the second and third trimesters of pregnancy.

OBJECTIVE: Routine malaria prophylaxis with chloroquine (CQ) is recommended to pregnant semi-immune women in several countries in Africa. The dosage is empirically based. We investigated whether blood CQ concentrations and apparent oral blood clearance (CL/F) change during the course of pregnancy. We also studied whether malaria parasites could be detected together with low CQ blood levels. METHODS: Forty nine semi-immune Tanzanian women were recruited in the 16th week of pregnancy. They were given 310 mg oral CQ base once per week as prophylaxis during the whole pregnancy. Capillary blood samples were taken for analysis of CQ before treatment and at weeks 26 and 36. Blood samples were dried on filter paper and analysed by HPLC. Blood was also drawn to detect occurrence of malaria parasites. RESULTS: A total of 25 women fulfilled the sampling schedule. CL/F increased significantly from 160 ml.min-1 at week 26 to 180 ml.min-1 at week 36. In 7 of 25 women, CL/F increased > 20%. Trough blood CQ concentrations, determined on four occasions at week 26 and at week 36 varied between 200 and 900 nmol.l-1. No statistically significant differences between occasions were seen. Malaria parasites were seen in two individuals early in pregnancy. CONCLUSION: Blood CQ CL/F showed a small increase during the course of pregnancy. The estimated mean blood CL/F values of 160 and 180 ml.min-1 (week 26 and 36, respectively) were higher than the mean CL/F of 125 ml.min-1 in non-pregnant individuals, published previously. Efficacy of higher dosages of CQ in malaria prophylaxis in pregnant women could, therefore, be evaluated in controlled trials in high-risk malaria areas.

The cardiovascular and central nervous system effects in the human of U-62066E. A selective opioid receptor agonist.

The cardiovascular and central nervous system effects of the kappa opioid receptor agonist U-62066E were investigated in ten normal male subjects who received U-62066E or placebo with low or high dose naloxone in a randomized, double blind study. Blood pressure and heart rate in the supine and standing position, plasma adrenaline and noradrenaline, regional Doppler blood velocity indices and psychometric assessments were recorded for 1.25 h before and 6 h following injection. U-62066E caused sedation and dysphoria but no euphoria. Plasma noradrenaline was increased by U62066E when compared with basal levels. This action of U62066E was prevented by high but not low dose naloxone. U-62066E had no significant effect on blood pressure, heart rate or regional blood flow indices in the vessels studied and no effect on plasma adrenaline levels. Since U62066E at a dose known to have marked kappa effects was not found to influence cardiovascular indices our results do not support a major role for kappa opioids in the control of the circulation. However, U62066E may influence noradrenaline release or clearance and cause sedation and psychotomimetic effects.

Mechanism of diuretic action of spiradoline (U-62066E)--a kappa opioid receptor agonist in the human.

1. The mechanism of the diuretic effect of the kappa opioid receptor agonist spiradoline was investigated in 10 healthy male subjects in a placebo-controlled, double-blind cross-over study. 2. Urine volume and osmolality, plasma vasopressin and Doppler renal blood velocity indices were recorded for 1.25 h before and 6 h following injection. 3. Spiradoline caused a significant increase in urine output which was antagonized by high but not low dose naloxone. The urine increase was accompanied by a significant decrease in osmolality which was also antagonised by high but not low dose naloxone. 4. Spiradoline had no effect on plasma vasopressin concentration or on renal blood velocity indices. 5. We conclude that kappa agonists induce diuresis in humans by a mechanism not involving suppression of vasopressin or changes in renal blood velocity indices.

Reproducibility of Doppler blood flow velocity waveform measurements: study on variability within and between day and during haemodynamic intervention in normal subjects.

Reproducibility of Doppler blood velocity waveform measurements in external and internal carotid, middle cerebral, and brachial arteries and ascending aorta was determined in 8 normal male volunteers twice daily on three occasions each separated by two or more weeks. Measurements were made in supine and standing positions at rest and after taking glyceryl trinitrate and in the supine position after performing a standardized exercise test. The Doppler blood flow waveform indices showed a between days coefficient of variation of less than 15% both for baseline measurements and during haemodynamic change induced by exercise or glyceryl trinitrate. We conclude that Doppler blood velocity waveform measurement in different vascular beds is reproducible at baseline and when the cardiovascular system is interrupted pharmacologically or physiologically.

The influence of food on the pharmacokinetics of 'biphasic' nifedipine at steady state in normal subjects.

Previous studies following single dose administration have suggested that the pharmacokinetics of various nifedipine formulations could be influenced by the timing of associated food consumption. In order more closely to reflect the clinical situation we have carried out a study at steady state using a 'biphasic' formulation comprising 'rapid' and 'retarded' drug release components. Fifteen normal subjects took 20 mg 'biphasic' nifedipine 12 hourly for 10 days. Studies were carried out on days 4, 7 and 10. On these days the nifedipine was taken 2 h or 1 h before or immediately following a light breakfast. A light breakfast influenced neither the rate nor the extent of nifedipine absorption nor the rate or extent of major metabolite appearance. We conclude that at steady state the timing of a light meal is unlikely to alter in any clinically important manner the pharmacokinetics of nifedipine released from 'biphasic' tablets.