Malaria detection

Detection by LDMS and structural elucidation of other secondary metabolite products, generated in the host during the onset of the parasite disease, is discussed. These molecules may serve as additional biomarkers for rapid malaria diagnosis by LDMS. For instance, choline phosphate (CP) is identified as the source of several low-mass ions observed in parasite-infected blood samples in addition to heme biomarker ions. The CP levels track the sample parasitemia levels. This biomarker can provide additional specificity and sensitivity when compared to malaria detection based on heme ion signals alone. Furthermore the observed elevated CP levels are discussed in the context of Plasmodium metabolism during its intra-erythrocytic life cycle. These data can... 

MALARIA DETECTION BY LASER DESORPTION MASS SPECTROMETRY... 

Choline Phosphate—Another Unique LDMS Biomarker for Malaria Detection... 

Gascoyne, P Satayaviviad, J. Ruchirawat, M. Microfluidic approaches to malaria detection. Acta. Tropica 2004, 89, 357-369. 

Recently, a novel physical method for rapid and sensitive malaria detection in blood has been developed [46-50]. This method— ultraviolet LD MS—is based on the detection of heme (iron protoporphyrin) in blood as a qualitative and quantitative malaria biomarker, both in vitro [46] and in vivo [49,50]. In infected erythrocytes, the parasite sequesters heme from digested hemoglobin in a molecular crystal (malaria pigment or hemozoin). LDMS detects only heme from hemozoin in parasite-infected blood, and not heme, bound to hemoglobin... 

Recent innovations for detecting malaria include DNA or RNA probes by polymerase chain reaction (PCR). These, however, are not widely available for clinical use. A rapid dipstick test (ParaSight F, Becton-Dickinson, Cockeyville, MD) reportedly has a sensitivity of 88% and a specificity of 97%, which is comparable to microscopy. However, ParaSight F can give false-positive results with rheumatoid factor thus microscopy remains the optimal test. 

Figure 8.2 Sample preparation protocols, currently employed in malaria parasite detection by LDMS. Both protocols require less than 50pl blood, obtained by either finger-stick or phlebotomy.

In the first LDMS-based detection of malaria in human subjects (unpublished), lOOpl P. falciparum or P. v/vax-infected blood samples, grouped into three different parasitemia ranges—low (10-150 parasites/pl), mid (2 x 103 parasites/pl), and high (25 x 103-60 x 103 parasites/pl)—have been examined using both sample preparation protocols. Parasitemia levels in these samples were previously determined independently for each sample by optical microscopy examination of blood smears. The LDMS data clearly indicate that... 

Demirev, P. A. Feldman, A. B. Kongkasuriyachai, D. Scholl, P. Sullivan, D. J. Kumar, N. Detection of malaria parasites by laser desorption mass spectrometry. 

Dean et al. [93] used a high performance liquid chromatographic method for the simultaneous determination of primaquine and carboxyprimaquine in plasma with electrochemical detection. After the addition of the internal standard, plasma was deproteinized by the addition of acetonitrile. Nitrogen-dried supernatants, resuspended in mobile phase were analyzed on a C8 reversed-phase column. Limits of detection for primaquine and carboxyprimaquine were 2 and 5 ng/mL with quantitation limits of 5 and 20 ng/mL, respectively. The assay sensitivity and specificity are sufficient to permit quantitation of the drug in plasma for pharmacokinetics following low dose (30 mg, base) oral administration of primaquine, typically used in the treatment of malaria and P. carinii pneumonia. 

Despite problems with its use, DDT has saved countless lives in regions where malaria is endemic. Tropical Asian countries, which have discontinued its use, have seen malaria incidence increase India and some other countries still cling to use of DDT because it is cheap and effective. Tissue levels in wildlife of the regions where DDT was banned began to decline about 10 years after DDT was banned however, DDT and its metabolites may routinely be detected in soil and bottom sediments even today (Galiulin and Bashkin, 1996). Over a long time, DDT is subject to atmospheric migration, for example from India to the Asian polar zone, to contribute to the contamination of local ecosystems as well. 

IgM may be regarded as the most primitive of the immunoglobulins. It is the first antibody produced in response to an antigen in the primary immune response. In human gestation it is the first Ig to be produced in the fetus in response to infection, e.g., syphilis, malaria, toxoplasmosis, and rubella in some of the lower vertebrates it is the only immunoglobulin as yet detected. 

It is now clear that fluorescent antibody to malaria persists for years after the patent malaria infestation has long disappeared, and malaria antibodies were still detectable in some West Africans after they had been in Britain for up to seven years (K5, V4). 

Deficiency of the first enzyme of the pentose phosphate pathway, glucose 6-phosphate dehydrogenase, is widespread.11 Its geographical distribution suggests that, like the sickle-cell trait, it confers some resistance to malaria. A partial deficiency of 6-phosphogluconolactonase (Eq. 17-12, step b) has also been detected within a family and may have contributed to the observed hemolytic anemia.1... 

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