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Biomedical subjects

L Rombo

Publications and source records attributed to L Rombo.

At least 55 records · Page 3Linked to original sources

Evaluation of test sensitivity and test specificity of three field methods for quantification of chloroquine in urine using liquid chromatography as reference method.

We have evaluated three quantitative colorimetric methods [bromthymol blue (BTB), Haskins, and Saker-Salomons (S-S)] for measurement of concentrations of chloroquine (CQ) in urine. A graphical evaluation of test sensitivity and test specificity at different concentrations of CQ in authentic urine samples was used. Liquid chromatography (LC) was used as a reference method. The Haskins method showed the highest test specificity (89%) and test sensitivity (97%), at a discrimination value of 2 mumols/L. At the same sensitivity (97%) as the Haskins method, S-S and BTB methods had test specificities of 49 and 13%, respectively. The correlation coefficients between the LC method and the colorimetric methods were all higher than 0.94 at a urinary concentration range of 2-100 mumols/L. The intra- and interassay variations for the colorimetric methods were all uniformly less than 15% at 2 mumols/L, but the Haskins method showed less variation than the other two methods.

Child↗

Changes in erythrocyte sedimentation rate, C-reactive protein and hematological parameters in patients with acute malaria.

Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and routine hematological parameters were reviewed in 258 patients with acute malaria and compared to a control group of 120 patients with other febrile illnesses after visiting malaria endemic areas. Thrombocytopenia was found in 80% of the malaria patients compared to 13% in controls (p less than 0.01). The malaria patients also had lower white blood cell counts and marginally lower hemoglobin values than control patients. No major differences were found in ESR or CRP values. Furthermore, there were no major differences in the hematological parameters between patients infected with different malaria species, or between patients with different ethnic background. Thrombocytopenia (platelet count less than 150 x 10(9)/l) had a predictive value positive of 56% and a predictive value negative of 95% for malaria in a febrile patient coming from an endemic area. Thus, the risk of malaria in a febrile thrombocytopenic patient coming from an endemic area was 56%, while the risk that another patient with a normal platelet count still had malaria was 5%.

Acute Disease↗

Response of Plasmodium falciparum to chloroquine treatment: relation to whole blood concentrations of chloroquine and desethylchloroquine.

A standard treatment with 25 mg chloroquine base per kilogram body weight was given to 39 semi-immune asymptomatic Tanzanian schoolchildren with Plasmodium falciparum parasitaemia. Whole blood chloroquine and desethylchloroquine concentrations were monitored 12 times during 30 days of follow-up using 100 microliters capillary blood dried on filter-paper. All but three children had detectable amounts of chloroquine (greater than or equal to 10 nmol/l) in their blood before treatment. The interindividual variations in concentrations during the first week were 3.3 to 5.1-fold for chloroquine and 3.5 to 6.3-fold for desethylchloroquine. In seven children with RII response in vivo, the highest determined chloroquine concentration was lower (P = 0.029) than in the others. After treatment, a rough approximation of the minimum inhibitory concentration in vivo was made by calculating the average of the chloroquine concentrations before and after the time when parasites increased or reappeared again. RII-resistant parasites increased in number when the median residual whole blood concentration in the children was approximately 790 (range, 444-869) nmol/l. Parasites reappeared when the median residual whole blood concentrations was approximately 147 (range, 44-673) nmol/l. We conclude that interindividual variations of chloroquine concentrations have an impact on the outcome of treatment and the classification of resistance in vivo.

Adolescent↗

Malaria prophylaxis with proguanil to Namibian refugee children in Angola.

Following a presumptive treatment with 35 mg chloroquine base/kg, 484 Namibian children between 5 months and 5 years of age received 50 mg of proguanil daily for 4 months. They were compared with 268 children living in a very adjacent area who received vitamin tablets after the initial chloroquine medication. Fewer fever episodes were recorded among the children who received proguanil and they were also requiring less presumptive treatments with chloroquine during the period of study, but there were only minor differences in parasite rate between the two groups at the end of the study period. Despite the reduction of morbidity, the required efforts were too large to justify another period of drug prophylaxis.

Angola↗

Sulfadoxine assay using capillary blood samples dried on filter paper--suitable for monitoring of blood concentrations in the field.

A high performance liquid chromatographic method for determination of sulfadoxine in whole blood obtained by finger prick and dried on filter paper is presented. The technique was validated by comparing the sulfadoxine concentration of simultaneously collected capillary blood dried on filter paper and conventional venous whole blood samples. Agreement between capillary blood dried on filter paper and venous whole blood was satisfactory. Limit of determination using 100 microliter of capillary blood was found to be 25 mumol/L (7.8 micrograms/ml). Sulfadoxine was stable in the dried filter papers for at least 15 weeks at +37 degrees C. The concentration ratio between plasma and whole blood of sulfadoxine was found to be approximately 1.8. The sampling technique on filter paper offers a convenient method for overcoming many of the practical problems of blood sampling in the field.

Capillaries↗

Chloroquine and desethylchloroquine concentrations during regular long-term malaria prophylaxis.

The concentrations of chloroquine and desethylchloroquine in the blood of 10 healthy adult Swedish volunteers who had been taking 310 mg chloroquine base once a week for at least 8 months for malaria prophylaxis were measured. Samples of capillary whole blood from the volunteers were dried on filter-paper and the drug and its principal metabolite determined by a specific high-performance liquid chromatography (HPLC) method. The day after taking the drug, the mean concentration of chloroquine and desethylchloroquine in whole blood were 1305 nmol/l and 915 nmol/l, respectively, and immediately before the next weekly dose, 489 nmol/l and 384 nmol/l, respectively. These are considered to be greater than the minimum inhibitory concentrations for susceptible strains but less than the maximum tolerated concentrations. The dosage of chloroquine recommended roughly 40 years ago for regular long-term prophylaxis should therefore not be changed.

Adult↗

Whole blood concentrations of chloroquine and desethylchloroquine during and after treatment of adult patients infected with Plasmodium vivax, P. ovale or P. malariae.

Whole blood concentrations of chloroquine and desethychloroquine were determined during and after chloroquine treatment of 15 adult patients infected with P. vivax, P. ovale or P. malariae. The median of chloroquine concentrations remained practically unchanged in samples drawn three hours after initiation of treatment and in samples drawn immediately before the next dose of chloroquine. Concentrations of chloroquine remained above 1.0 mumol/litre for at least four days. The calculated sum of chloroquine and desethylchloroquine concentrations was above 1.0 mumol/litre for at least seven days. These concentrations are regarded as sufficient for treatment of P. vivax, P. ovale and P. malariae infections.

Adult↗

In vivo response of Plasmodium falciparum to different doses of chloroquine in semi-immune children in Liberia, West Africa.

The efficacy of different doses of chloroquine in suppressing patent parasitaemia was investigated in 326 children two to 12 years old, living in six villages with holoendemic malaria. The children were given single doses (2, 3, 5-7 or 9-12 mg base kg-1) or a standard treatment over three days (25 mg base kg-1). Parasite prevalences were recorded after one, two, three, four, six and eight weeks. Complete clearance of Plasmodium falciparum trophozoites (TC) by day 7 was achieved by a dosage of 9-12 mg kg-1. By probit analysis of log dose response, 50% clearance (TC50) was established at about 1.5 mg kg-1, whereas a TC95 required 5.5 mg kg-1. The reappearance of patent parasitaemia was dependent on the dose of chloroquine given and on malaria transmission. After the standard dose treatment, only one re-infection in 56 children appeared within 21 days despite high sporozoite inoculation rates in the area. The dosage of 9-12 mg kg-1 yielded a hundredfold reduction of mean parasite density in the children if calculated over a four-week period. It may represent a suitable monthly regimen in a malaria control scheme in a holoendemic area with high P. falciparum sensitivity to chloroquine.

Child↗

Sensitivity in vivo of Plasmodium falciparum to chloroquine and pyrimethamine/sulfadoxine in a coastal area of Tanzania.

The in vivo response of Plasmodium falciparum to chloroquine and to pyrimethamine/sulfadoxine was studied for seven days in schoolchildren from two villages 30 to 40 km north of Dar es Salaam. Standard therapeutic regimen of chloroquine (25 mg base kg-1) failed to clear parasitaemia in 17 of 62 (27%) treated subjects. In contrast, standard treatment with pyrimethamine/sulfadoxine cleared the parasitaemia in all 44 treated subjects within five days. Hence, in the studied area, the therapeutic effect of sulfadoxine/pyrimethamine was superior to that of chloroquine.

Adolescent↗

Monthly antimalarial chemotherapy to children in a holoendemic area of Liberia.

Two hundred and eighty-two children, two to nine years old, were included in a prospective three-year study in four villages with holoendemic malaria. In three villages the children received monthly doses of either chloroquine, pyrimethamine or chlorproguanil respectively for two years. In the fourth, vitamin tablets were used as placebo. Presumptive treatment with chloroquine (10 mg base kg-1) was given to all children with fever of suspected malarial origin. The two-year drug distribution was satisfactorily fulfilled to 168 children. Surveys, including physical and laboratory examinations were performed every six months, four weeks after medication. A fifth village was only visited at the start of the study and after two years. The mean crude parasite rate was initially 92%. Plasmodium falciparum was the main species. Splenomegaly was recorded in all children. In the chloroquine-treated children, the parasite rates varied between 30% and 50% during the study. By the end of the second year the spleen rate was reduced from 100% to 50%. Reported episodes of fever were reduced to half and mean haematocrit levels increased by 6% in comparison with children receiving the placebo. Total IgG concentrations were reduced from 36.7 g l-1 to 25.9 g l-1, whereas no significant decrease was observed in malarial seropositivity as measured by indirect immunofluorescence. Chlorproguanil had a weaker impact on parasitaemia with parasite rates between 50% and 90%. However, the spleen rate was reduced to 67% and there was a significant reduction of reported fever episodes. Mean haematocrits increased by 4%. Total IgG decreased from 31.8 g l-1 to 23.8 g l-1. In contrast, in the pyrimethamine group, the placebo group and the untreated group from the fifth village, the malariometric indices after two years were comparable to each other and to the initial values. During the third year only presumptive chloroquine treatment was given, and by the end of the study all malariometric indices were again comparable. From clinical observations there was no apparent impairment of protective immunity to malaria from the two years of regular distribution of the drugs. We conclude that a certain degree of malaria control could be achieved in Liberian children by the administration of monthly doses of chloroquine 10 mg base kg-1. The administration of chlorproguanil (1.5 mg kg-1) represents an alternative regimen.

Antimalarials↗