Sanjeev Krishna

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BACKGROUND The borders of Thailand harbour the world's most multidrug resistant Plasmodium falciparum parasites. In 1984 mefloquine was introduced as treatment for uncomplicated falciparum malaria, but substantial resistance developed within 6 years. A combination of artesunate with mefloquine now cures more than 95% of acute infections. For both treatment(More)
BACKGROUND Increasing drug resistance limits the choice of efficacious chemotherapy against Plasmodium falciparum malaria in Africa. Amodiaquine still retains efficacy against P falciparum in many African countries. We assessed the safety, treatment efficacy, and effect on gametocyte carriage of adding artesunate to amodiaquine in three randomised trials in(More)
Artemisinins are extracted from sweet wormwood (Artemisia annua) and are the most potent antimalarials available, rapidly killing all asexual stages of Plasmodium falciparum. Artemisinins are sesquiterpene lactones widely used to treat multidrug-resistant malaria, a disease that annually claims 1 million lives. Despite extensive clinical and laboratory(More)
Infections with the malaria parasite Plasmodium falciparum result in more than 1 million deaths each year worldwide. Deciphering the evolutionary history and genetic variation of P. falciparum is critical for understanding the evolution of drug resistance, identifying potential vaccine candidates and appreciating the effect of parasite variation on(More)
BACKGROUND Our study examined the relative contributions of host, pharmacokinetic, and parasitological factors in determining the therapeutic response to artemether-lumefantrine (AL). METHODS On the northwest border of Thailand, patients with uncomplicated Plasmodium falciparum malaria were enrolled in prospective studies of AL treatment (4- or 6-dose(More)
OBJECTIVE Artemether-lumefantrine (AL), presently the most favoured combination therapy against uncomplicated Plasmodium falciparum malaria in Africa, has recently shown to select for the pfmdr1 86N allele. The objective of this study was to search for the selection of other mutations potentially involved in artemether-lumefantrine tolerance and/or(More)
Rapid diagnosis and accurate quantification of Plasmodium falciparum parasitemia are important for the management of malaria. The assessment of disease severity also depends on evaluation of metabolic indexes such as blood glucose and lactate concentrations. Here we describe an accurate and rapid alternative to conventional thick film examination (Lambaréné(More)
Aquaporin-4 (AQP4) is the major water channel in the brain, expressed predominantly in astroglial cell membranes. Initial studies in AQP4-deficient mice showed reduced cellular brain edema following water intoxication and ischemic stroke. We hypothesized that AQP4 deletion would have the opposite effect (increased brain swelling) in vasogenic (noncellular)(More)
Brain edema accounts for much of the morbidity and mortality associated with common neurological conditions such as head trauma, brain tumors, stroke and liver failure. Treatment options are limited to osmotic agents such as mannitol, surgical decompression, and other maneuvers, none of which correct the molecular-level mechanisms responsible for brain(More)
The clinical and laboratory features of severe falciparum malaria in 180 Gambian children were studied between 1985 and 1989. Of the 180 children, 118 (66%) presented with seizures, 77 (43%) had cerebral malaria, 35 (20%) had witnessed seizures after admission, 29 (16%) were hypoglycemic, and 27 (15%) died. Respiratory distress was a common harbinger of a(More)