Intravenous Artesunate for Severe Malaria

OBJECTIVE: To review the pharmacodynamics and pharmacotherapeutic use of intravenous artesunate for the treatment of severe malaria. DATA SOURCES: Literature was retrieved through PubMed (1999 March 2010), MEDLINE (1996 March 2010), and the Centers for Disease Control and Prevention (CDC), using the search terms artemisinin, artesunate, malaria, and severe malaria. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles in English that were identified from the data sources were reviewed. Focus was placed on post-marketing trials examining the safety and efficacy of artesunate in comparison with other regimens. DATA SYNTHESIS: The treatment of severe malaria requires prompt, safe, and effective intravenous antimalarials. Many oral and intravenous agents are available worldwide for the treatment of malaria; however, quinidine has been the only option for parenteral therapy in the US. Furthermore, this product\u27s lack of availability as well as its adverse safety profile have created a treatment option gap. Recently, intravenous artesunate was approved by the Food and Drug Administration (FDA) for investigational drug use and distribution by the CDC. Three major studies regarding the use of intravenous artesunate are reviewed, in addition to the World Health Organization\u27s malaria treatment guidelines. While there are no published head-to-head trials of intravenous artesunate versus intravenous quinidine for severe malaria, several international studies comparing intravenous quinine and artesunate concluded that artesunate has the highest treatment success, with lower incidence of adverse events. In addition, other literature is reviewed regarding counterfeit and other issues associated with artesunate. CONCLUSIONS: Artesunate, a new antimalarial currently available through the CDC, appears to be highly effective, better tolerated than quinidine, and not hampered by accessibility issues. If it were to be FDA approved and commercially available, it would be the preferred agent for the treatment of severe malaria in the US

Maximum of the Riemann zeta function on a short interval of the critical line

We prove the leading order of a conjecture by Fyodorov, Hiary and Keating, about the maximum of the Riemann zeta function on random intervals along the critical line. More precisely, as T→∞ for a set of t∈[T,2T] of measure (1−o(1))T, we have max|t−u|≤1log∣∣ζ(12+iu)∣∣=(1+o(1))loglogT

Serologic Evidence of Lyssavirus Infections among Bats, the Philippines

Active surveillance for lyssaviruses was conducted among populations of bats in the Philippines. The presence of past or current Lyssavirus infection was determined by use of direct fluorescent antibody assays on bat brains and virus neutralization assays on bat sera. Although no bats were found to have active infection with a Lyssavirus, 22 had evidence of neutralizing antibody against the Australian bat lyssavirus (ABLV). Seropositivity was statistically associated with one species of bat, Miniopterus schreibersi. Results from the virus neutralization assays are consistent with the presence in the Philippines of a naturally occurring Lyssavirus related to ABLV

Maximum of the Riemann zeta function on a short interval of the critical line

We prove the leading order of a conjecture by Fyodorov, Hiary and Keating, about the maximum of the Riemann zeta function on random intervals along the critical line. More precisely, as T→∞ for a set of t∈[T,2T] of measure (1−o(1))T, we have max|t−u|≤1log∣∣ζ(12+iu)∣∣=(1+o(1))loglogT