Plasmodium falciparum histidine rich protein 2 (PfHRP2) antigen was measured semi-quantitatively in whole blood, plasma, and supernatants and red blood cells of cultures in vitro using the dipstick ParaSight-F test and also by a quantitative antigen-capture enzyme-linked immunosorbent assay (ELISA). In vitro, PfHRP2 was secreted mainly during the second half of the asexual cycle with a marked rise during schizont development and rupture. The total PfHRP2 secreted before schizogony corresponded to approximately 4% of that contained in the red blood cells. In samples from 55 patients with acute falciparum malaria, the level of detection by ELISA corresponded to parasitaemias of 100/microL for whole blood and 1600/microL for separated plasma. Whole blood PfHRP2 levels were correlated significantly with admission parasitaemia (r = 0.76, P < 0.0001) and the stage of parasite development (r = 0.43, P < 0.01). Although whole blood PfHRP2 concentrations were higher in severe malaria, plasma concentrations of PfHRP2 were considerably higher in severe malaria (median titre 1:320, range zero to 1:1280) than in uncomplicated malaria (median titre 1:5, range zero to 1:80; P < 0.0001). The ratio of whole blood to plasma PfHRP2 was lower in severe than in uncomplicated malaria (median 4, range 0.25 to 256, versus 64, range 4 to 1280; P < 0.0001). With plasma samples the intensity of colour change on the dipstick correlated well with more precise measurement of optical density in the ELISA (r = 0.88, P < 0.0001). These results suggest that measurement of PfHRP2 in plasma could provide an alternative approach to the assessment of the parasite biomass, and thus prognosis, in severe malaria, and that this could be done simply by using the currently available dipsticks.

Adolescent↗

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Estimating Plasmodium vivax parasitaemia.

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Animals↗

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Artesunate and mefloquine in the treatment of uncomplicated multidrug-resistant hyperparasitaemic falciparum malaria.

Oral artesunate is the most effective treatment for uncomplicated hyperparasitaemia in falciparum malaria. To assess the contribution of mefloquine to therapeutic efficacy in an area endemic for mefloquine-resistant Plasmodium falciparum, an open randomized comparison of a 5 d course of oral artesunate (total dose 12 mg/kg) with and without a single dose of mefloquine (25 base mg/kg) was conducted in 100 adults and children with uncomplicated hyperparasitaemia (> 4% parasitized red blood cells). Both regimens were well tolerated and gave equally rapid clinical responses (84% of patients were aparasitaemic and 96% were afebrile within 48 h), but the recrudescence rate assessed at day 42 was 6% in those receiving artesunate with mefloquine compared to 36% in those receiving artesunate alone (adjusted hazard ratio 7, 95% confidence interval [95% CI] 2-32; P < 0.01). In addition, the efficacy of a 7 d course of artesunate, with and without the addition of mefloquine, was monitored in 178 patients who were not part of the randomized comparison. The failure rate was again lower in those receiving artesunate and mefloquine--7% (95% CI 2-13) compared with 26% (95% CI 8-44) in patients treated with artesunate alone. An oral regimen of 5 d or more of artesunate, together with mefloquine (25 mg/kg) given on day 2, is an effective treatment for uncomplicated hyperparasitaemic falciparum malaria in this area of high level multidrug resistance.

Administration, Oral↗

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HIV RNA quantitation: marker of HIV infection.

Assessment of the status and prognosis of an HIV-infected individual traditionally has been difficult for the clinician. The use of markers of disease progression such as CD4+ has been found to not be a complete indicator of the status of an HIV-infected individual. As a result, determining appropriate therapy for the treatment of this viral infection has been both unpredictable and challenging. Recent development of a laboratory assay has brought a new tool in the management of HIV. The assay is a quantitation of the amount of detectable HIV RNA and estimates the amount of HIV viral load or HIV viral burden present in the blood. Since the development of this assay, HIV RNA quantitation has rapidly become an important surrogate marker of HIV infection. In addition, this quantitation is used to determine the effectiveness of anti-HIV therapies. Understanding the differences and results of quantitative assays is imperative in the management of HIV-infected patients. This article summarizes the events leading to the creation of quantitative assays, explanations and comparisons of the current quantitative assays, and nursing considerations for the implications and uses of viral load markers.

Biomarkers↗

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Congo red birefringent structures in the hypothalamus in senile dementia of the Alzheimer type.

Serial cryostat sections of hypothalamus from four cases of Alzheimer-type dementia and four controls were stained with Congo red and examined for birefringence. Green birefringence and dichroism was associated with (a) neurofibrillary tangles, which were most numerous at the level of the tuberomammillary nucleus where they were found in large acetylcholinesterase-positive neurons; (b) neuropil processes within tangle fields; (c) a few plaque cores in the mammillary body; (d) spicules at the ependyma of the third ventricle, and (e) blood vessels. Birefringence (e) had different properties from (a) to (d) and was considered to be due to collagen. The ependymal spicules did not react with an antibody which recognized the tangles and neuropil processes. Each Alzheimer case had many more tangles than the control cases. Birefringence in (b)-(d) tended to be greater in the Alzheimer than in the control cases. This study confirms previous reports of large numbers of tangles in circumscribed areas of caudal hypothalamus in Alzheimer-type dementia and demonstrates that Congo red staining reveals abnormalities in hypothalamic structures (neuropil processes and ependyma) not demonstrated by other staining techniques.

Aged↗

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Locally determined performance related pay.

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Employee Performance Appraisal↗