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Biomedical subjects

D Warhurst

Publications and source records attributed to D Warhurst.

17 recordsLinked to original sources

Efficacy of artesunate plus pyrimethamine-sulphadoxine for uncomplicated malaria in Gambian children: a double-blind, randomised, controlled trial.

BACKGROUND: Resistance to cheap effective antimalarial drugs, especially to pyrimethaminesulphadoxine (Fansidar), is likely to have a striking impact on childhood mortality in sub-Sharan Africa. The use of artesunate (artesunic acid) [corrected] in combination with pyrimethamine-sulphadoxine may delay or prevent resistance. We investigated the efficacy, safety, and tolerability of this combined treatment. METHODS: We did a double-blind, randomised, placebo-controlled trial in The Gambia. 600 children with acute uncomplicated Plasmodium falciparum malaria, aged 6 months to 10 years, at five health centres were randomly assigned pyrimethaminesulphadoxine (25 mg/500 mg) with placebo; pyrimethamine-sulphadoxine plus one dose of artesunate (4mg/kg bodyweight); or pyrimethamine-sulphadoxine plus one dose 4 mg/kg bodyweight artesunate daily for 3 days. Children were visited at home each day after the start of treatment until parasitaemia had cleared. FINDINGS: The combined treatment was well tolerated. No adverse reactions attributable to treatment were recorded. By day 1, only 178 (47%) of 381 children treated with artesunate were still parasitaemic, compared with 157 (81%) of 195 children in the pyrimethamine-sulphadoxine alone group (relative risk 1.7 [95% CI 1.5-2.0], p<0.001). Treatment-failure rates at day 14 were 3.1% in the pyrimethamine sulphadoxine alone group, and 3.7% in the one-dose artesunate group (risk difference -0.6% [-4.2 to 3.0]) and 1.6% in the three-dose group (1.5 [1.5-4.5], p=0.048). Symptoms resolved faster in children who received artesunate, but there was no additional benefit for three doses of artesunate over one dose. Children given artesunate were less likely to be gametocytaemic after treatment. INTERPRETATION: The combined treatment was safe, well tolerated, and effective. The addition of artesunate to malaria treatment regimens in Africa results in lower gametocyte rates and may lower transmission rates.

Animals↗

The effect of chemoprophylaxis on the timing of onset of falciparum malaria.

The association between chemoprophylaxis and delayed onset of falciparum malaria was investigated in a retrospective study of 477 nonimmune cases reported to the UK Malaria Reference Laboratory (MRL) who had used either mefloquine (n = 56), chloroquine-proguanil (n = 90) or no chemoprophylaxis (n = 331). For holiday and short-term travellers using mefloquine the time between arrival in the UK and diagnosis was found to be significantly longer than for chloroquine and proguanil (C-P) users or for those who had not used prophylaxis at all (P < 0.004). This delay was primarily due to a later onset of symptoms. C-P use was not associated with delay in onset of symptoms or diagnosis when compared to not using prophylaxis. Possible reasons for the findings are discussed. Mefloquine may continue to exert a partially suppressive effect on resistant strains of Plasmodium falciparum (Pf). That chloroquine with proguanil was not found to have such an effect may be due to poor compliance to proguanil or differences in the mode of action and range of parasite resistance to the two regimens. Differences in drug compliance may be one reason why only mefloquine users on holiday or short-term journeys experienced delays to onset of disease. Drug compliance amongst cases of breakthrough malaria on chemoprophylaxis may be lower than is generally recognized. It is important for clinicians and travellers to be aware that the onset of falciparum malaria may be delayed by mefloquine prophylaxis.

Antimalarials↗

Microbiological quality in Finnish public swimming pools and whirlpools with special reference to free living amoebae: a risk factor for contact lens wearers?

To assess the possible risk of microbial keratitis associated with swimming or bathing in public pools, the microbiological quality as well as the presence of free living amoebae in 16 halogenated swimming pools and whirlpools, located in Helsinki, Finland, was determined. Five additional whirlpools situated in the ferries cruising from Finland to Sweden were included in the study. Other parameters investigated were the total bacterial count, identification of Pseudomonas aeruginosa and Staphylococcus aureus, measurement of free residual and combined chlorine, potassium permanganate index, urine, pH, and turbidity. Amoebae were detected in 41% of the pool water samples studied. Seven of 11 whirlpools and four of 10 swimming pools were shown to contain amoebae. An Acanthamoeba species was isolated from only one outdoor swimming pool; the other amoebae belonged to the genera Vexillifera, Flabellula, Hartmannella, and Rugipes. Although not a single verified case of Acanthamoeba keratitis has been found in Finland, the findings show that there is a theoretical risk of amoebic and bacterial keratitis associated with swimming or bathing in properly cleaned public pools. Consequently, we do not recommend swimming or bathing with contact lenses.

Amoeba↗

Malaria imported into the United Kingdom in 1992 and 1993.

A total of 1,629 cases of malaria were reported in the United Kingdom in 1992, and 1,922 cases in 1993, fewer than the peak of 2,332 reached in 1991. Of the 3,551 cases of malaria reported during 1992 and 1993, 74 were reported from Scotland, 45 from Wales, and 13 from Northern Ireland. Fourteen people died of falciparum malaria in the two years, 12 of whom contracted the disease in Africa and two in India. Preventive measures were inadequately followed by 12 of the 14 patients who died, eight of whom took no prophylaxis at all, and diagnosis was delayed in the other two. Over a third of the malaria cases were immigrants from endemic areas who had settled in the United Kingdom and who travelled to visit friends and relations. This was the commonest reason for travel given by cases, and correlates with a marked rise in falciparum malaria in settled immigrants from West Africa.

Adult↗

Association of Vibrio cholerae with fresh water amoebae.

An investigation was undertaken to determine whether Acanthamoeba polyphaga SHI and Naegleria gruberi 1518/1e could affect the survival of various strains of Vibrio cholerae in laboratory microcosms. In microcosms pre-inoculated with trophozoites of amoebae, all six strains of V. cholerae tested survived and multiplied during 24 h. In control microcosms without trophozoites of amoebae, survival of the V. cholerae strains was much decreased. Two strains of V. cholerae were used to determine whether V. cholerae might survive ingestion within amoebae and subsequent encystment. Strain 152 was re-isolated from encysting N. gruberi 1518/1e but not from A. polyphaga SHI. Strain 9112 could not be isolated from cysts of either species of amoebae.

Acanthamoeba↗

Application of a capture enzyme immunoassay in an outbreak of waterborne giardiasis in the United Kingdom.

A capture enzyme immunoassay (EIA) for the detection of Giardia lamblia antigen was used to examine 136 fecal samples collected during an outbreak of waterborne giardiasis in a city in the UK. Six cases of Giardia lamblia infection were detected that had previously not been diagnosed by microscopy. The capture EIA provides an efficient means of processing large numbers of samples for prompt and accurate assessment of an epidemic. It may also facilitate rapid tracing of epidemic sources.

Antigens, Protozoan↗

Acanthamoeba keratitis--resistance to medical therapy.

Successful medical therapy of Acanthamoeba keratitis has been reported with combination therapy; topical Brolene and neomycin. Resistance has not so far been identified as a problem, but was the basis for recurrent disease observed in a patient with bilateral infection. Eradication of amoebae was finally achieved following prolonged topical therapy and two corneal grafts in each eye. Topical anti-amoebic therapy with paromomycin, benzethonium chloride, clotrimazole and R11/29 (a phenanthridinium compound), was continued for three months post-operatively. No further recurrences occurred during 14 months' follow-up. Drug sensitivities were performed for three isolates of Acanthamoeba sp (group II) which demonstrated the development of resistance to Brolene and arsenic. In addition, the resistant isolates were temperature-sensitive mutants which would not grow at temperatures above 30 degrees C. This could explain 'culture-negative' results in some cases of clinical recurrence when incubation of laboratory samples had only been performed at 37 degrees C.

Acanthamoeba Keratitis↗

An enzyme-linked immunosorbent assay for the detection of Entamoeba histolytica antigens in faecal material.

This paper describes a method for the detection of Entamoeba histolytica antigens in stool samples using a multi-layer ELISA. The method is sensitive and specific, showing no interference with other intestinal parasites, e.g. E. coli, E. hartmanni, Endolimax nana, Iodamoeba buetschlii, Hymenolepis nana, Giardia lamblia, Trichomonas and Ascaris. The method provides a rapid and simple screening assay for E. histolytica infections and should assist in diagnosis and epidemiological studies of the disease.

Animals↗

Acanthamoeba keratitis successfully treated medically.

The first medical cure of a corneal infection due to an Acanthamoeba species is reported. The 44-year-old patient developed a suppurative keratitis associated with an epithelial defect, hypopyon, and secondary glaucoma. Acanthamoeba was confirmed as the causative agent four months after presentation when positive cultures were obtained from the cornea and from the conjunctiva. Sensitivity studies of the isolated organism were performed, and the infection was successfully controlled by treatment with a combination of dibromopropamidine and propamidine isethionate ointment and drops and neomycin drops. Keratoplasty was performed 22 months after onset, and no viable acanthamoebae were present in the resected tissue, though possible cyst remnants were identified by immunofluorescent techniques.

Adult↗