*Some Selected Abstracts:*
1.	Balunas MJ, Kinghorn AD. Drug discovery from medicinal plants. Life Sci. 2005 Dec 22;78(5):431-41. Review. Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, 833 South Wood Street, University of Illinois at Chicago, Chicago, IL 60612, USA. Current research in drug discovery from medicinal plants involves a multifaceted approach combining botanical, phytochemical, biological, and molecular techniques. Medicinal plant drug discovery continues to provide new and important leads against various pharmacological targets including cancer, HIV/AIDS, Alzheimer's, malaria, and pain. Several natural product drugs of plant origin have either recently been introduced to the United States market, including arteether, galantamine, nitisinone, and tiotropium, or are currently involved in late-phase clinical trials. As part of our National Cooperative Drug Discovery Group (NCDDG) research project, numerous compounds from tropical rainforest plant species with potential anticancer activity have been identified. Our group has also isolated several compounds, mainly from edible plant species or plants used as dietary supplements, that may act as chemopreventive agents. Although drug discovery from medicinal plants continues to provide an important source of new drug leads, numerous challenges are encountered including the procurement of plant materials, the selection and implementation of appropriate high-throughput screening bioassays, and the scale-up of active compounds.
2.	Barennes H, Valea I, Nagot N, Van de Perre P, Pussard E. Sublingual sugar administration as an alternative to intravenous dextrose administration to correct hypoglycemia among children in the tropics.Pediatrics. 2005 Nov;116(5):e648-53. Centre Muraz, Bobo-Dioulasso, Burkina Faso, France. hubert.barennes@avf.org BACKGROUND: Hypoglycemia is a common determining factor of poor prognosis for children with severe malaria in sub-Saharan Africa. Intravenous dextrose administration is rarely available. Oral mucosal delivery may be an alternative to parenteral administration. A randomized, clinical trial was performed in Burkina Faso among moderately hypoglycemic children, comparing sublingual sugar administration with oral water, oral sugar, and dextrose infusion administrations. METHODS: Sixty-nine children with glucose concentrations of < 0.8 g/L were assigned randomly to 1 of 4 methods of administration, 1 with 3 different doses of sugar, as follows: oral group (OG) (n = 15): 2.5 g of sugar; sublingual group (SG) (n = 27): 2.5 g of sugar under the tongue, with 3 treatment subgroups, ie, 0.1 g/kg, 0.15 g/kg, and 0.2 g/kg; intravenous group (IG) (n = 8): 8 mL of 30% dextrose in a single bolus; water group (n = 11). Eight children received sublingual sugar twice, ie, 0.1 g/kg at baseline and 20 minutes later. Blood glucose concentrations were measured every 20 minutes for 80 minutes. Treatment failures, peak glucose concentrations, times to glucose concentration normalization, and kinetic profiles were evaluated. RESULTS: No treatment failures were observed in the SG and IG, compared with 8 (53%) and 9 (81.8%) failures in the OG and water group, respectively. SG children exhibited glucose kinetic profiles and bioavailabilities (77%, 99%, and 81% in the 3 SG groups) similar to those of IG children. Bioavailabilities were 84% and 38% in the SG and OG, respectively. Children > 7 years of age required repeated sublingual administrations to maintain normoglycemia. CONCLUSIONS: The sublingual administration of sugar proved to be effective among moderately hypoglycemic children. It is a simple and promising method to control hypoglycemia among children in both developing and developed countries. This pediatric practice should be investigated in more detail among children with severe malaria.
3.	Lemnge MM, Ali AS, Malecela EK, Sambu E, Abdulla R, Juma MS, Fakih K, Abdulla KH, Njau RJ. Therapeutic efficacy of sulfadoxine-pyrimethamine and amodiaquine among children with uncomplicated Plasmodium falciparum malaria in Zanzibar, Tanzania. Am J Trop Med Hyg. 2005 Oct;73(4):681-5. National Institute for Medical Research, Amani Medical Research Centre, Amani, Tanga, Tanzania. mlemnge@amani.mimcom.net The efficacy of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) was assessed at Kivunge and Micheweni in Zanzibar, Tanzania, in 2001. The main objective was to obtain baseline data after observations of high levels of chloroquine treatment failures. Children (6-59 months) were randomized to receive either drug. At Kivunge, SP and AQ were given to 64 and 63 cases, while for Micheweni, 61 and 70 cases were treated. Main findings were overall high rates (> 90%) of adequate clinical response (ACR) with AQ. A lower ACR was seen in the SP group at Kivunge (87.1%) compared with Micheweni (94.8%). Furthermore, in the ACR group, 16.7% AQ parasitological resistance (RI-RIII) was encountered at Kivunge. Most of the cases of SP parasitological resistance (14.5%; RI/RII) were seen at Micheweni. Notwithstanding this, the overall treatment failure was only 9.2% with SP and 5.5% with AQ. The Zanzibar Ministry of Health has since reviewed its antimalarial drug policy.
4.	Mehta M, Sonawat HM, Sharma S. Malaria parasite-infected erythrocytes inhibit glucose utilization in uninfected red cells. FEBS Lett. 2005 Nov 7;579(27):6151-8. Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400 005, India. The erythrocytic stages of the malaria parasite depend on anaerobic glycolysis for energy. Using [2-13C]glucose and nuclear magnetic resonance, the glucose utilization rate and 2,3-diphosphoglycerate (2,3-DPG) level produced in normal RBCs and Plasmodium falciparum infected red blood cell populations (IRBCs, with <4% parasite infected red cells), were measured. The glucose flux in IRBCs was several-folds greater, was proportional to parasitemia, and maximal at trophozoite stage. The 2,3-DPG levels were disproportionately lower in IRBCs, indicating a downregulation of 2,3-DPG flux in non-parasitized RBCs. This may be due to lowered pH leading to selective differential inhibition of the regulatory glycolytic enzyme phosphofructokinase. This downregulation of the glucose utilization rate in the majority (>96%) of uninfected RBCs in an IRBC population may have physiological implications in malaria patients.
5.	Richer J, Chudley AE. The hemoglobinopathies and malaria. Clin Genet. 2005 Oct;68(4):332-6. Review. Department of Pediatrics and Child Health, Program in Genetics and Metabolism, Children's Hospital, University of Manitoba, Winnipeg, Manitoba, Canada. With philatelic illustrations, we review sickle cell anemia, some of the common hemoglobinopathies, and their relevance to malaria. We discuss the mechanism by which hemoglobinopathies arise, the progress made with pre-natal screening, as well as innovative therapies. We review recent developments in the pathophysiology of malaria and discuss innovations in the effort against this parasite.
6.	Williams TN, Mwangi TW, Wambua S, Peto TE, Weatherall DJ, Gupta S, Recker M, Penman BS, Uyoga S, Macharia A, Mwacharo JK, Snow RW, Marsh K. Negative epistasis between the malaria-protective effects of alpha+-thalassemia and the sickle cell trait. Nat Genet. 2005 Nov;37(11):1253-7. Kenya Medical Research Institute/Wellcome Trust Programme, Centre for Geographic Medicine Research, Coast, PO Box 230, Kilifi District Hospital, Kilifi, Kenya. twilliams@kilifi.mimcom.net The hemoglobinopathies, disorders of hemoglobin structure and production, protect against death from malaria. In sub-Saharan Africa, two such conditions occur at particularly high frequencies: presence of the structural variant hemoglobin S and alpha(+)-thalassemia, a condition characterized by reduced production of the normal alpha-globin component of hemoglobin. Individually, each is protective against severe Plasmodium falciparum malaria, but little is known about their malaria-protective effects when inherited in combination. We investigated this question by studying a population on the coast of Kenya and found that the protection afforded by each condition inherited alone was lost when the two conditions were inherited together, to such a degree that the incidence of both uncomplicated and severe P. falciparum malaria was close to baseline in children heterozygous with respect to the mutation underlying the hemoglobin S variant and homozygous with respect to the mutation underlying alpha(+)-thalassemia. Negative epistasis could explain the failure of alpha(+)-thalassemia to reach fixation in any population in sub-Saharan Africa.

Diagnosis, Diagnostics, Immunodiagnosis & Immunodiagnostics:

13919. Afenyadu GY, Agyepong IA, Barnish G, Adjei S. Improving access to early treatment of malaria: a trial with primary school teachers as care providers. Trop Med Int Health. 2005 Oct;10(10):1065-72.

13920. Ashley EA, White NJ. Artemisinin-based combinations. Curr Opin Infect Dis. 2005 Dec;18(6):531-6. Review.

13921. Chung WY, Gardiner DL, Hyland C, Gatton M, Kemp DJ, Trenholme KR. Enhanced invasion of blood group A1 erythrocytes by Plasmodium falciparum. Mol Biochem Parasitol. 2005 Nov;144(1):128-30.

13922. Ginsburg H. Should chloroquine be laid to rest? Acta Trop. 2005 Oct;96(1):16-23. Review.

13923. Heppner DG Jr, Walsh DS, Uthaimongkol N, Tang DB, Tulyayon S, Permpanich B, Wimonwattrawatee T, Chuanak N, Laoboonchai A, Sookto P, Brewer TG, McDaniel P, Eamsila C, Yongvanitchit K, Uhl K, Kyle DE, Keep LW, Miller RE, Wongsrichanalai C. Randomized, controlled, double-blind trial of daily oral azithromycin in adults for the prophylaxis of Plasmodium vivax malaria in Western Thailand. Am J Trop Med Hyg. 2005 Nov;73(5):842-9.

13924. Kundu R, Ganguly N, Ghosh TK, Choudhury P, Shah RC. Diagnosis and management of malaria in children: recommendations and IAP plan of action. Indian Pediatr. 2005 Nov;42(11):1101-14.

13925. Lesho EP, George S, Wortmann G. Fever in a returned traveler. Cleve Clin J Med. 2005 Oct;72(10):921-7. Review.

13926. Okocha E C, Ibeh C C, Ele P U, Ibeh N C. The prevalence of malariaparasitaemia in blood donors in a Nigerian teaching hospital. Jvector borne Dis 2005; 42(1): 21-4.

13927. Villamor E, Msamanga G, Aboud S, Urassa W, Hunter DJ, Fawzi WW. Adverse perinatal outcomes of HIV-1-infected women in relation to malaria parasitemia in maternal and umbilical cord blood. Am J Trop Med Hyg. 2005 Oct;73(4):694-7.

Pathogenesis:

13928. Adam I, Elbashir MI. Comments on "Risk factors for malaria infection and anemia for pregnant women in the Sahel area of Bandiagara, Mali" by A. Dicko et al. [Acta Trop. 89 (2003) 17-23]. Acta Trop. 2005 Oct;96(1):60-1.

Therapy:

13929. Boctor FN. Red blood cell exchange transfusion as an adjunct treatment for severe pediatric falciparum malaria, using automated or manual procedures. Pediatrics. 2005 Oct;116(4):e592-5.

13930 Dunavan CP. Tackling malaria. Sci Am. 2005 Dec;293(6):76-83.

13931. Hutchinson OC, Cunningham AA. Benefits and risks in malaria control. Science. 2005 Oct 7;310(5745):49-51; author reply 49-51.

13932. Khan MA, Mekan SF, Abbas Z, Smego RA Jr. Concurrent malaria and enteric fever in Pakistan. Singapore Med J. 2005 Nov;46(11):635-8.

13933. Okie S. Betting on a malaria vaccine. N Engl J Med. 2005 Nov 3;353(18):1877-81.

13934. The Lancet. Support for antimalaria efforts will depend on results. Lancet. 2005 Dec 3;366(9501):1904.

13935. Vogel G. Infectious diseases. Cracks in the first line of defense. Science. 2005 Dec 9;310(5754):1607.

13936. Ward MD, Selgrade MK. Benefits and risks in malaria control. Science. 2005 Oct 7;310(5745):49-51; author reply 49-51.

13937. Zarocostas J. Health experts gather to step up fight against malaria. BMJ. 2005 Oct 29;331(7523):986.