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Biomedical subjects

L Rombo

Publications and source records attributed to L Rombo.

At least 73 records · Page 4Linked to original sources

Evaluation of three qualitative tests for detection of chloroquine in urine--agreement with plasma concentrations determined with liquid chromatography.

Three qualitative tests for detection of chloroquine in urine were compared and evaluated against concomitant plasma concentrations determined with liquid chromatography. All urine tests from five volunteers taking a single dose of 5 mg chloroquine base kg-1 were positive for at least ten days with the Haskins test, and for at least three days with the Wilson Edeson test. Even on the first day, the Dill-Glazko test indicated chloroquine in the urine of one volunteer only. After a single dose of 10 mg kg-1 to five other volunteers the Haskins test was uniformly positive for 14 days while the Wilson Edeson test was positive for four days. The Dill-Glazko test was positive for one day only. No false negative results were obtained with the Haskins test when plasma concentrations were above 0.03 mumol 1(-1), as compared to 0.11 mumol 1(-1) with the Wilson Edeson test. The Dill-Glazko test was uniformly positive when plasma concentrations were above 0.38 mumol 1(-1). The Dill-Glazko test was affected by low urinary pH and by addition of erythrocytes to urine. We conclude that the Dill-Glazko test should not be used.

Chloroquine↗

Concentrations of chloroquine and desethylchloroquine in capillary blood dried on filter paper during and after treatment of Tanzanian children infected with Plasmodium falciparum.

Chloroquine and desethylchloroquine concentrations were determined in capillary whole blood dried on filter paper. The samples were obtained from 20 Tanzanian children before, during and after standard treatment of Plasmodium falciparum malaria with a total dose of 25 mg chloroquine base/kg. Samples were obtained before each dose and then daily up to one week after initiation of treatment. Chloroquine concentrations were consistently above 1.0 micromol/L only on the day after termination of treatment. The inter-individual range of area under the curve (AUC) was 5.6 fold for chloroquine and 8.8 fold for desethylchloroquine. The AUC and elimination time of chloroquine and desethyl-chloroquine was less than the median in two children with persisting parasitemia despite treatment. Thus, pharmaco-kinetics of chloroquine in the individual might be important to consider when P. falciparum parasites are classified in different categories of resistance.

Adolescent↗

Different malaria control activities in an area of Liberia--effects on malariometric parameters.

The epidemiology of malaria was studied in a West African mining town (Yekepa) and three surrounding zones defined as Close, Middle and Far areas. Malariometric parameters were investigated in children two to nine years of age at the end of the rainy season. In Yekepa, vector control measures and intense suppression of malaria with drugs had created an almost hypoendemic situation with a spleen rate of 11%. In Close area, vector control was applied to some extent and malaria drugs were frequently used for treatment; the spleen rate was 40%. In Middle area, a mobile clinic provided sporadic malaria treatment to small children, but the clinic did not reach out to Far area. The spleen rates were 95 and 99%, respectively. Three species of Plasmodium were found in all areas. The prevalences in Far area were P. falciparum 82%, P. malariae 39% and P. ovale 9%. The crude parasite rates increased from 13% in Yekepa to 92% in Far area, whereas haematocrit levels decreased from 37.6 to 35.2, respectively. Plasmodium falciparum seropositivity, as measured by indirect immunofluorescence, was 74% in Yekepa and 99% in Middle and Far areas. Total IgG concentrations ranged from 18 g1(-1) in Yekepa to 33 g1(-1) in Far area. Three main anopheline species were found in the zones outside Yekepa. Their relative frequencies in Far area were Anopheles funestus 45%, A. hancocki 37%, and A. gambiae 18%. The local inoculation rates gradually increased outwards from Yekepa from less than 0.01 to 0.17 inoculations per man and night at the beginning of the dry season.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Susceptibility of Plasmodium falciparum to chloroquine in northern Liberia after 20 years of chemosuppression and therapy.

The in vivo and in vitro susceptibility of Plasmodium falciparum to chloroquine was investigated in northern Liberia after 20 years of continuous chemosuppression and therapy with 4-aminoquinolines. In all patients studied (n = 53) parasitaemias were cleared within four days. There were no recrudescences in 16 patients followed-up for 28 days. All isolates of P. falciparum tested in vitro (n = 26) showed sensitive patterns. Schizont maturation was inhibited by a chloroquine concentration of between 0.25 and 0.75 mumol-1. In this area of Liberia no resistance to chloroquine was found in spite of extensive use of 4-aminoquinolines. This may support the view that importation of at least partially resistant strains, rather than local mutation of P. falciparum, precedes selection of resistant strains. Hence, we conclude that regular intake of chloroquine by groups at risk is justified if it is combined with regular monitoring of drug susceptibility.

Child↗

Determination of chloroquine and its desethyl metabolite in whole blood: an application for samples collected in capillary tubes and dried on filter paper.

A high performance liquid chromatography method for analysis of chloroquine and desethylchloroquine was adapted for 75 microliters aliquots of whole blood obtained by finger-prick and dried on filter paper. The precision of the method was satisfactory at whole blood concentrations of 40 nmol/L (coefficient of variation, 5%). The dried samples were stable for at least 7 weeks at 20 degrees C. The concentrations in venous whole blood and in dried samples correlated well. The correlation coefficient was 0.99 for chloroquine and 0.97 for desethylchloroquine. Chloroquine concentrations were marginally but significantly higher in venous whole blood. When fitted to a linear equation (y = bx + a) the relationship was y = 0.96x + 0.03. Desethylchloroquine concentrations did not differ significantly in venous whole blood and in finger-prick blood dried on filter paper. The method is specific and sensitive enough for pharmacokinetic studies and can be used in areas with limited technical facilities.

Blood Specimen Collection↗

Chloroquine and desethylchloroquine in plasma, serum, and whole blood: problems in assay and handling of samples.

A spectrophotofluorometric method for determination of chloroquine in body fluids was compared with a recently developed high performance liquid chromatographic (HPLC) method. The spectrophotofluorometric method was found to codetermine the main metabolite desethylchloroquine and thus to give higher "chloroquine" concentrations than the HPLC method. The concentrations determined with spectrophotofluorometry roughly corresponded to the calculated sum of chloroquine and desethylchloroquine as determined with the HPLC method. The concentrations of chloroquine and desethylchloroquine were higher in serum, and considerably higher in whole blood, than in plasma. The duration and force of centrifugation greatly influenced the concentrations of chloroquine and desethylchloroquine found in plasma. The concentrations decreased as centrifugal force increased reaching relatively stable levels at 500 g. Increasing the centrifugation time partly compensated for lower g forces. These methodological problems can be avoided by using whole blood for determinations of chloroquine. Since the biological activities of desethylchloroquine and chloroquine are not the same, drug monitoring should be performed with a method distinguishing between the parent drug and the metabolite.

Blood Specimen Collection↗

Malaria control by chlorproguanil. I. Clinical effects and susceptibility of Plasmodium falciparum in vivo after seven years of monthly chlorproguanil administration to children in a Liberian village.

For seven years, chlorproguanil (1.0 to 2.0 mg kg-1) was administered monthly to the children below 15 years of age in a village with holoendemic malaria. Malariometric indices were recorded every six months. Susceptibility in vivo was monitored by the clearance of Plasmodium falciparum parasitaemia after drug intake. Three parasite species were found initially: P. falciparum (52%), P. malariae (8%) and P. ovale (4%). The parasites found during the study were mainly P. falciparum, and parasite rates ranged from 37 to 87% at the different surveys one month after respective drug intake. A fifty-fold decrease of mean parasite density was generally observed seven days after drug intake. Splenomegaly was initially recorded in all two to nine year old children, with a mean size of 2.64 according to Hackett's index. From 18 months onwards as the mean spleen index was 1.15 in the same age group. Chlorproguanil may represent an important alternative drug to groups at risk in malaria control schemes.

Adolescent↗

Is the working capacity of Liberian industrial workers increased by regular malaria prophylaxis?

In a study of the impact of malaria prophylaxis upon the physical working capacity of Liberian industrial workers, two groups of men, one with and the other without malaria prophylaxis, were compared over a period of one year. At the beginning and at the end of the study, the haemoglobin concentration, haematocrit, blood volume and physical performance--measured by bicycle ergometry and expressed as work load at heart rate 170--were compared. No significant differences were found, either within or between the two groups. Routinely distributed malaria prophylaxis thus seems to be of little importance with respect to working capacity in this type of community, where malaria is meso-endemic.

Blood Volume↗

On the question of dose-dependent chloroquine elimination of a single oral dose.

Subjects (n = 45) were randomly given single oral doses of 2 (n = 11), 3 (n = 9), 5 (n = 8), 10 (n = 10), or 15 mg/kg (n = 7) chloroquine base. Chloroquine was analyzed by HPLC in serum samples taken at 3 to 168 hr after dosing. AUCs, calculated for the time period of 0 to 168 hr were proportional to the doses. Mean AUC value increased 6.7 times when the dose was increased 7.5 times (from 2 to 15 mg/kg). These data do not support the existence of significant capacity-limited chloroquine elimination within the dose range studied.

Adolescent↗

A case-control study in northern Liberia of Plasmodium falciparum malaria in haemoglobin S and beta-thalassaemia traits.

A case-control study was carried out on 558 patients with malaria attending a hospital in Yekepa, northern Liberia; 94 patients (16.8%) were aged at least ten years, probably because of a low level of protective immunity in town dwellers due to malaria control. The proportion of sickle cell traits (1.8%) among the patient group was lower than in the population (7.2%) served by the hospital (chi 2, 21.455, 1 df, P less than 0.001). A stratified analysis showed the relative risk for Plasmodium falciparum malaria in sickle cell trait over normal homozygotes, as 0.29 (upper 95%) confidence interval, 0.56). For beta-thalassaemia trait, the proportion among patients was 5.5% as against 9.0% in the general population (chi 2, 6.158, 1 df, 0.025 greater than P greater than 0.010). Stratified analysis gave a weighted relative risk for beta-thalassaemia heterozygotes of 0.49 (upper 95% confidence interval, 0.74). Although there were four beta-thalassaemia traits in the 10-14 year stratum with moderate to high parasitaemias, we consider that the overall results are consistent with relative resistance against P. falciparum malaria of both sickle cell and beta-thalassaemia heterozygotes in this population. No conclusions were possible from this investigation with regard to HbC and the malaria hypothesis. We found no evidence that P. falciparum malaria elevates HbA2 concentrations into the beta-thalassaemia range.

Adolescent↗