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W Rooney

Publications and source records attributed to W Rooney.

30 records · Page 2Linked to original sources

In vitro sensitivity of multiresistant Plasmodium falciparum to new candidate antimalarial drugs in western Thailand.

The present study, carried out in 1987 in Thailand, has been designed to validate the in vitro microtest system, standardized by the World Health Organization (WHO), for the new antimalarials pyronaridine and halofantrine. The sensitivity of naturally acquired, multiresistant populations of Plasmodium falciparum has been assessed in order to develop a data base for further longitudinal investigations. For both drugs the in vitro microtest system seems to be suitable. The concentration range of plates can be considered as almost ideal for pyronaridine (0.1-6.40 mumol/l) while for halofantrine (0.002-0.128 mumol/l) an upward extension of the concentration range would be appropriate. Validation studies with artemisinin demonstrated the need for revising the protocol for the production of the dosing solutions. In the light of current knowledge about therapeutic concentration levels it would probably be appropriate to adopt a range of 0.2-12.8 mumol/l. All tested isolates, except possibly three, showed sensitive responses to pyronaridine. The high EC99 value of halofantrine could be indicative of some resistance to this drug. Rank correlation analysis suggested cross-resistance of pyronaridine and chloroquine which could be of consequence for the future introduction of pyronaridine.

Animals↗

Detection of Plasmodium falciparum infection in human patients: a comparison of the DNA probe method to microscopic diagnosis.

We have previously reported the isolation and testing of a DNA probe specific for the detection of Plasmodium falciparum. Field studies to compare the sensitivity and specificity of the DNA probe with that of light microscopy have been performed. In 2 studies in Thailand, 1,397 patients were tested. Microscope slides were prepared in a standard fashion and examined by clinical technicians and expert microscopists. The DNA probe method compares favorably in sensitivity with routine microscopy, detecting parasite densities as low as 40 parasites/microliters blood in the first study and, after modifications, 20-25 parasites/microliters blood in the second. Modifications included the elimination of salt from the lysis buffer, increasing the pH of the lysis buffer, and use of nylon based hybridization membranes instead of nitrocellulose. The DNA probe method offers the advantage of a standardized procedure that can be used in a batchwise fashion on a large number of samples.

Adolescent↗

Evidence of increased chloroquine sensitivity in Thai isolates of Plasmodium falciparum.

Sensitivity of Thai isolates of Plasmodium falciparum to chloroquine collected over the years 1978-1986 was measured by two methods: (i) by growth of previously cultured isolates for 72 h in presence of drug, and (ii) by the WHO standard in vitro microtest. During this period there were signs of a gradual increase in drug sensitivity, coinciding with the withdrawal of chloroquine for treatment of falciparum malaria in Thailand.

Animals↗

Response of Plasmodium falciparum infections to pyrimethamine-sulfadoxine in Thailand.

The results of this study in Thailand indicate that the early response of falciparum infections to a single dose of pyrimethamine-sulfadoxine is influenced by the developmental stages of the parasite present at the time of treatment. Parasite clearance is slower when young rings predominate at the time of treatment. This should be taken into account when considering the clinical management of patients and the comparative efficacy of antimalarials in clearing parasites from the peripheral blood. The 36-48 hr delay in schizonticidal action observed after treatment of febrile infections and the associated decline in blood concentrations of pyrimethamine suggest that a single dose may not be the ideal way of administering this drug combination and may encourage the emergence of drug-resistant parasites.

Adult↗

Specific DNA probe for the diagnosis of Plasmodium falciparum malaria.

Malaria can be diagnosed either by direct microscopic examination of blood smears, which is time consuming and requires expertise, or by immunological techniques, which are effective but do not distinguish between past and present infections. In this study, a simple procedure was developed for spotting lysed blood from infected patients directly onto nitrocellulose paper and identifying the malaria species on the basis of hybridization of parasite DNA with a species-specific probe. A genomic DNA library of Plasmodium falciparum was screened to detect clones containing DNA sequences that are highly repeated within the parasite genome. Several such clones were further analyzed to identify those that hybridize specifically with P. falciparum DNA but not with DNA from humans, P. vivax, or P. cynomolgi. This technique appears to be sensitive enough to detect 10 picograms of purified P. falciparum DNA (equivalent to 100 parasites) and in field studies is able to detect approximately 40 parasites per microliter of blood.

Cloning, Molecular↗

Sensitivity to quinine and mefloquine of Plasmodium falciparum in Thailand.

Between 1982 and 1984 a regimen consisting of quinine and tetracycline was routinely used in Thailand to treat outpatients with microscopically confirmed falciparum malaria. Due to compliance problems associated with the 7-day multiple-dose regimen, there was a recrudescence rate of approximately 30%. Studies carried out in 1982 and 1984 in four areas of Thailand indicated that there was a significant decrease in the sensitivity of Plasmodium falciparum to quinine. A significant, though less marked, reduction in the sensitivity of P. falciparum to the structurally related drug mefloquine was also observed, although this compound was not operationally deployed in Thailand before 1985. These findings emphasize the need to replace the long multiple-dose quinine regimen by an effective, acceptable, single-dose treatment.

Antimalarials↗

Use of the in vitro microtechnique for the assessment of drug sensitivity of Plasmodium falciparum in Sennar, Sudan.

In 1978, studies on the chloroquine sensitivity of Plasmodium falciparum were carried out in the district of Sennar, Sudan. The results of the in vivo tests showed parasites resistant at the RI level only, but the mean clearance time of trophozoites from the blood was higher than for strains found in many other areas of tropical Africa. The in vitro tests, using the microtechnique, indicated a lower sensitivity to chloroquine in the local P. falciparum isolates than in those of most other African countries. However, similar results have been reported from Ethiopia. The chloroquine sensitivity of P. falciparum from Sennar is close to the critical level of resistance. The in vitro microtechnique was also used to test for the sensitivity to Dabequin, 4-aminobenzo-quinoline, and was generally found to be a suitable and reproducible method, with a greater potential than the standard macro method. At parasite densities of over 100 000 asexual parasites per microlitre of blood the effect of a given concentration of chloroquine was related to the parasite density owing to the selective uptake of the compound by the parasitized cells.

Adolescent↗

A field trial of the ParaSight-F test for the diagnosis of Plasmodium falciparum infection.

The rapid manual ParaSight-F test for Plasmodium falciparum is an antigen capture test detecting trophozoite-derived histidine rich protein II, is simple and provides a definitive diagnosis within 10 min. Compared with 913 thick blood film examinations, the ParaSight-F test had 93.4% sensitivity and 98.2% specificity. Compared with 520 blood samples within the same study examined with the aid of the polymerase chain reaction, the ParaSight-F test had 91.6% sensitivity and 99.4% specificity. The ParaSight-F test could be a valuable diagnostic tool for falciparum malaria in any situation requiring rapid diagnosis in the absence of microscopical examination.

Animals↗

ParaSight-F test for the detection of treatment failure in multidrug resistant Plasmodium falciparum malaria.

The ParaSight-F test for the detection of Plasmodium falciparum was evaluated for its accuracy and usefulness in predicting treatment outcome in 75 patients (70 males, 5 females) with acute uncomplicated malaria who attended a malaria clinic in Mae Sot, Tak province, on the Thai-Myanmar border. All patients were admitted to the clinic for 28 d to exclude reinfection. The test was performed using blood samples collected into ethylenediaminetetraacetic acid from the patients on admission, and on days 1, 2, 7, and 14. The presence of microscopically detectable parasitaemia was used as the reference for sensitivity and specificity of the test. The reappearance of parasites on day 28 was used to determine the accuracy of predicting the outcome of artemether treatment on day 14. The sensitivity of the ParaSight-F test on admission, and on days 1, 2, 7, and 14, was 98.7%, 96.7%, 100%, 100% and 100%, respectively, with corresponding specificities of 50%, 24.2%, 47.1% and 72.9%. The sensitivity for predicting recrudescence by using the test on day 14 was 100%, with 97.7% specificity, and the sensitivity of predicting a sensitive response on day 14 was 97.7%, with 100% specificity. The test seems to permit more precise detection of treatment failure under 'field' conditions if used on day 14 after the start of treatment.

Animals↗

Sensitivity in vitro of Plasmodium falciparum to three currently used antimalarial drugs on the western border of Thailand.

The sensitivity in vitro of Plasmodium falciparum to mefloquine, quinine and artemisinin was assessed in an area of multi-drug resistance on the Thai-Myanmar border, using the World Health Organization's microtest, based on schizont maturation inhibition. Participating individuals were exclusively those who had contracted their infections within Myanmar. A total of 34 successful tests were carried out for mefloquine and quinine, showing a marked decrease in sensitivity compared to previously published results. Ten artemisinin tests were successful, with many failures due to the poor storage stability of the test plates. The implications of the shelf-life of the artemisinin plates is discussed. These results contribute to setting a base line of sensitivity to artemisinin in vitro.

Adolescent↗