Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case was a 28-year-old Japanese female who was considered to be infected with malaria in India. She manifested fever in Tokyo, Japan, and was brought to Toho University Hospital due to continuous high fever and severe thrombocytopenia. Ring forms at 11% of her RBCs and ICT Malaria P.f/P.v test was also positive for Plasmodium falciparum diagnosis. Not only the high parasitemia and delay of the diagnosis (6 days after the onset of fever), but also her DIC status required prompt and proper treatment. The diagnosis of severe malaria was strongly considered, and intravenous Artesunate (a qinghaosu derivative) was decided to be administered to the patient. After the four series of administration, mefloquine was subsequently given to prevent recrudescence. Parasite clearance time and fever clearance time were 24 hours and 108 hours, respectively. Thrombocytopenia was improved shortly after the treatment, but then anemia was once worsened with following gradual improvement. No other significant side effects were observed and no recrudescence occurred up to 8 months after her discharge. In Japan, very few cases treated with intravenous Artesunate were reported and our results showed its safe and excellent effect for a Japanese malaria patient.
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PMID:[A case of falciparum malaria successfully treated with intravenous artesunate]. 1244 49

In an open-label trial carried out on the northwest border of Thailand, 1596 patients with uncomplicated multidrug-resistant falciparum malaria were randomly assigned to receive atovaquone-proguanil, atovaquone-proguanil-artesunate, or artesunate-mefloquine and were followed up for 42 days. All 3 regimens were highly effective and well tolerated. Fever duration and parasite clearance times were significantly shorter among patients who received artesunate (P<.001). Polymerase chain reaction genotyping confirmed that recrudescence occurred in 13 patients who received artesunate-mefloquine (2.4%), 5 who received atovaquone-proguanil-artesunate (0.9%), and 15 who received atovaquone-proguanil (2.8%). Adding artesunate to atovaquone-proguanil reduced the risk of failure 3-fold (95% confidence interval [CI], 1.1-8.2) and subsequent gametocyte carriage 21-fold (95% CI, 14-30). Gastrointestinal complaints in the first 48 h after initiation of treatment were more common among artesunate recipients, but after day 2, dizziness, sleep disturbance, nausea, vomiting, and anorexia were more common among mefloquine recipients (P< or =.014). Artesunate-atovaquone-proguanil is a highly effective and well-tolerated treatment for multidrug-resistant falciparum malaria.
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PMID:Treatment of uncomplicated multidrug-resistant falciparum malaria with artesunate-atovaquone-proguanil. 1247 69

Artesunate, a semi-synthetic derivative of a naturally occurring anti-malarial artemisinin was compared with chloroquine in C57BL/6 mice infected with Plasmodium berghei Anka (PbA). A 7-day oral administration of artesunate prevented parasitaemia at 10 mg/kg/day. However, recrudescence of parasitaemia and cerebral malaria occurred upon cessation of treatment followed by death within 28 days. However, a 14-day course of artesunate (100 mg/kg/day) prevented completely the development of parasitaemia and cerebral malaria with a survival of more than 60-days as did 10 mg/kg/day chloroquine. These data demonstrate that oral artesunate inhibits PbA and prevents cerebral malaria, but needs to be administered at high dose and for prolonged time to eradicate PbA infection in mice.
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PMID:Oral artesunate prevents Plasmodium berghei Anka infection in mice. 1254 47

Artesunate is one of the most important antimalarial agents available, since it is effective against parasites that have developed resistance to conventional antimalarials in sub-Saharan Africa. Antimalarial combination chemotherapies with artesunate (4 mg/kg of body weight once daily for 3 days) as one partner have been proposed. However, the efficacy of a 3-day course of artesunate alone has never been evaluated in individuals in Africa (which has 90% of the worldwide malaria burden) living in regions of hyperendemicity, where a considerable degree of immunity might substantially enhance the efficacy of short courses of artesunate compared to those in regions where the levels of endemicity are low. This lack of information does not permit a systematic assessment of the value of artesunate-based combination chemotherapies in Africa. Therefore, we studied the efficacy and safety of a 3-day course of artesunate (4 mg/kg of body weight, orally, once daily) for the treatment of uncomplicated Plasmodium falciparum malaria in Gabonese patients aged 4 to 15 years (n = 50). Artesunate was well tolerated, and no severe adverse event was reported. Parasite elimination was rapid and was achieved in all patients within < or =72 h (geometric mean time to elimination, 34 h). The PCR-corrected cure rate by day 14 was 92% (46 of 50 patients), but it dropped to 72% (36 of 50 patients) by day 28. We conclude that a 3-day course of artesunate fails to achieve sufficiently high cure rates for uncomplicated falciparum malaria in Gabonese children.
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PMID:Short-course artesunate treatment of uncomplicated Plasmodium falciparum malaria in Gabon. 1260 19

A randomized, open-label comparison of artesunate and quinine was conducted in 113 adults with clinically severe falciparum malaria in western Thailand. Mortality was 12% with artesunate and 22% with quinine treatment (relative risk, 0.53; 95% confidence interval, 0.23-1.26; P=.22). Multiple logistic regression analysis found admission plasma lactate level, Glasgow Coma Scale score, and total serum bilirubin level to be independent risk factors for death. Coma recovery and times to normalize plasma lactate levels were similar, but the parasite clearance time was much shorter among artesunate-treated patients (P=.019). Fewer patients became hypoglycemic during artesunate therapy (10%) than during quinine therapy (28%) (P=.03). Artesunate is at least as effective as quinine in the treatment of adults with severe malaria. Larger trials are required to determine whether mortality is reduced among patients treated with artesunate.
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PMID:Randomized comparison of artesunate and quinine in the treatment of severe falciparum malaria. 1283 Apr 3

The activities of primaquine in combination with quinine or artesunate against asexual- and sexual-stage parasites were assessed in 176 adult Thai patients with uncomplicated Plasmodium falciparum malaria. Patients were randomized to one of the six following 7-day oral treatment regimens: (i) quinine alone, (ii) quinine with tetracycline, (iii) quinine with primaquine at 15 mg/day, (iv) quinine with primaquine at 30 mg/day, (v) artesunate alone, or (vi) artesunate with primaquine. Clinical recovery occurred in all patients. There were no significant differences in fever clearance times, rates of P. falciparum reappearance, or recurrent vivax malaria between the six treatment groups. Patients treated with artesunate alone or in combination with primaquine had significantly shorter parasite clearance times (mean +/- standard deviation = 65 +/- 18 versus 79 +/- 21 h) and lower gametocyte carriage rates (40 versus 62.7%) than those treated with quinine (P < or = 0.007). Primaquine did not affect the therapeutic response (P > 0.2). Gametocytemia was detected in 98 patients (56% [22% before treatment and 34% after treatment]). Artesunate reduced the appearance of gametocytemia (relative risk [95% confidence interval] = 0.34 [0.17 to 0.70]), whereas combinations containing primaquine resulted in shorter gametocyte clearance times (medians of 66 versus 271 h for quinine groups and 73 versus 137 h for artesunate groups; P < or = 0.038). These results suggest that artesunate predominantly inhibits gametocyte development whereas primaquine accelerates gametocyte clearance in P. falciparum malaria.
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PMID:Activities of artesunate and primaquine against asexual- and sexual-stage parasites in falciparum malaria. 1504 37

Artesunate (ART) is a semi-synthetic derivative of the sesquiterpene artemisinin used for the second line therapy of malaria infections with Plasmodium falciparum. ART also inhibits growth of many transformed cell lines. In the present investigation, we show that ART inhibited the growth of normal human umbilical endothelial cells and of KS-IMM cells that we have established from a Kaposi's sarcoma lesion obtained from a renal transplant patient. The growth inhibitory activity correlated with the induction of apoptosis in KS-IMM cells. Apoptosis was not observed in normal endothelial cells, which, however, showed drastically increased cell doubling times upon ART treatment. ART strongly reduced angiogenesis in vivo in terms of vascularization of Matrigel plugs injected subcutaneously into syngenic mice. We conclude that ART represents a promising candidate drug for the treatment of the highly angiogenic Kaposi's sarcoma. As a low-cost drug, it might be of particular interest for areas of Kaposi's sarcoma endemics. ART could be useful for the prevention of tumor angiogenesis.
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PMID:Inhibition of angiogenesis in vivo and growth of Kaposi's sarcoma xenograft tumors by the anti-malarial artesunate. 1554 82

Artesunate was introduced in Thailand in 1995 for the treatment of falciparum malaria in areas of multidrug resistance, where it is used in combination with mefloquine. The studies were conducted between May and August 1999, 2000 and 2001 in the provinces Mae Hong Son and Tak (Mae Sot District) in northwestern Thailand, both on the border to Myanmar. The province of Mae Hong Son is still largely unaffected by multidrug resistance and infections with Plasmodium falciparum are treated with mefloquine alone. In the district of Mae Sot, 350 km southwards, more than 60% of the Plasmodium falciparum isolates were found to be resistant to mefloquine. Between 1999 and 2001, a total of 227 fresh isolates of Plasmodium falciparum were successfully tested for their sensitivity to artemisinin using the WHO standard in vitro microtest. The weighted mean EC5o and EC90 values for 1999-2001 were 9.20 nM and 34.37 nM in Mae Hong Son and 11.18nM and 71.63nM in Mae Sot, respectively. The comparison of the sensitivity to artemisinin between Mae Hong Son and Mae Sot showed no significant difference in 1999, but significant differences in 2000 (p<0.05) and in 2001 (p<0.01). This phenomenon could be a consequence of different drug pressure. Furthermore, the lower sensitivity of Plasmodium falciparum to mefloquine in Mae Sot may play a minor (but amplifying) role, as the activities of artemisinin and mefloquine show a significant correlation.
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PMID:Comparative study of the in vitro sensitivity of Plasmodium falciparum to artemisinin in two border areas of Thailand. 1568 41

There has been a relentless increase in resistance of malaria parasites to conventional antimalarial drugs, including chloroquine, sulfadoxine-pyrimethamine and mefloquine. In response to this situation, short-course artemisinin-based combination therapies (ACTs) have been developed. The World Health Organization has endorsed ACT as first-line treatment where the potentially life-threatening parasite Plasmodium falciparum is the predominant infecting species. ACTs combine the rapid schizontocidal activity of an artemisinin derivative (artesunate, artemether or dihydroartemisinin) with a longer-half-life partner drug. Although the use of chloroquine and sulfadoxine-pyrimethamine as partners in ACT improves their efficacy, this may only have value as a short-term measure in patients with a degree of immunity to malaria. Alternative currently available partner drugs include mefloquine, lumefantrine and piperaquine. Artesunate-mefloquine is highly effective but is expensive and side effects (mainly neurotoxicity) can be problematic. Artemether-lumefantrine, the only ACT available in Australia, appears less effective than artesunate-mefloquine and needs to be administered with food to ensure adequate bioavailability. Dihydroartemisinin-piperaquine is highly effective, well tolerated and relatively inexpensive. The goal of potent, safe, easy-to-administer and inexpensive ACTs may see trioxolanes in place of artemisinin derivatives, as well as novel partner drugs such as pyronaridine or naphthoquine, in the future.
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PMID:Artemisinin-based combination therapies for uncomplicated malaria. 1572 Jan 66

In addition to their well-known anti-malarial activity, artemisinin and its derivatives (1,2,4-trioxanes) possess potent activity against tumor cells in the nano- to micromolar range. Candidate genes that may contribute to the sensitivity and resistance of tumor cells to artemisinins were identified by pharmacogenomic and molecular pharmacological approaches. Target validation was performed using cell lines transfected with candidate genes or corresponding knockout cells. These genes are from classes with different biological function; for example, regulation of proliferation (BUB3, cyclins, CDC25A), angiogenesis (vascular endothelial growth factor and its receptor, matrix metalloproteinase-9, angiostatin, thrombospondin-1) or apoptosis (BCL-2, BAX). Artesunate triggers apoptosis both by p53-dependent and -independent pathways. Anti-oxidant stress genes (thioredoxin, catalase, gamma-glutamyl-cysteine synthetase, glutathione S-transferases) as well as the epidermal growth factor receptor confer resistance to artesunate. Cell lines over-expressing genes that confer resistance to established anti-tumor drugs (MDR1, MRP1, BCRP, dihydrofolate reductase, ribonucleotide reductase) were not cross-resistant to artesunate, indicating that this drug has a different target and is not subject to multidrug resistance. The Plasmodium translationally controlled tumor protein (TCTP) represents a known target protein of artemisinin and its derivatives in the malaria parasite. The microarray-based mRNA expression of human TCTP correlated with sensitivity to artesunate in tumor cells, suggesting that human TCTP contributes to response of tumor cells to the drug. The multi-factorial nature of cellular response to artemisinin and its derivatives may be beneficial to treat otherwise drug-resistant tumors and may explain why resistance development has not been observed in either cancer or malaria.
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PMID:Mechanistic perspectives for 1,2,4-trioxanes in anti-cancer therapy. 1587 3


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