Medicine and Health Sciences Commons^™

Inhibition Of Yeast Hexokinase By The Antimalarial Drug Artemisinin: Probing Mechanism Of Action With A Model Enzyme, Jennifer S. Spence

Biological Sciences Theses & Dissertations

A leading infectious cause of death, malaria threatens approximately half of the world's population, and drug-resistant strains of Plasmodium falciparum have created immense difficulty in chemotherapy of the disease. The artemisinin (ART) class of antimalarials may represent a powerful solution. In addition to their safety, effectiveness, and moderate cost, they are the only drugs in use for which there has been no widespread evidence of clinical resistance. The exact parasiticidal mechanism of ART is highly contested, but evidence suggests that protein alkylation may play a role in cytotoxicity. in vitro essays were performed using yeast hexokinase (HK) to demonstrate a …

Situasi Malaria Di Kabupaten Lebak, Fauzul Hayat, Nia Kurniatillah

Kesmas

Pada periode 2002-2006, di Kabupaten Lebak, API tergolong Middle Case Incidence (MCI), dengan nilai rata-rata (2.87%) dan berada pada kisaran 2.04-4.51%. Dari 35 wilayah kerja puskesmas terdapat enam wilayah endemis yang meliputi puskesmas Malimping, Binuangeun, Bayah, Cihara, Panggarangan dan Cilograng. Ada wilayah kerja puskesmas yang dilaporkan dengan klasifikasi MCI. Penderita positif malaria cenderung meningkat secara fluktuatif dengan puncak yang tidak jelas, kasus positif malaria tertingi ditemukan pada bulan Februari, Maret, Mei, Juli dan Desember. Tingkat infeksi malaria yang tinggi pada kelompok populasi ditentukan berdasarkan proporsi sediaan darah positif malaria dari sediaan darah yang diperiksa dengan angka SPR 006 rata-rata 12.64%, …

Using Decision Analysis To Improve Malaria Control Policy Making, Jonathan B. Wiener, Randall A. Kramer, Katherine L. Dickinson, Richard M. Anderson, Vance G. Fowler, Marie Lynn Miranda, Clifford M. Mutero, Kathryn A. Saterson

Faculty Scholarship

Malaria and other vector-borne diseases represent a significant and growing burden in many tropical countries. Successfully addressing these threats will require policies that expand access to and use of existing control methods, such as insecticide-treated bed nets (ITNs) and artemesinin combination therapies (ACTs) for malaria, while weighing the costs and benefits of alternative approaches over time. This paper argues that decision analysis provides a valuable framework for formulating such policies and combating the emergence and re-emergence of malaria and other diseases. We outline five challenges that policy makers and practitioners face in the struggle against malaria, and demonstrate how decision …

Analysis Of The Malaria Vaccine Potential Of Plasmodium Falciparum Merozoite Surface Protein-3, Stephen James Jordan

All ETDs from UAB

Malaria causes an estimated 1-3 million deaths each year, with the majority of deaths being a result of infection with Plasmodium falciparum. No commercially available vaccine currently exists, but multiple subunit-based vaccines are in development including one based on the promising vaccine candidate P. falciparum Merozoite Surface Protein-3 (PfMSP3). PfMSP3 varies in sequence between P. falciparum isolates, but all variation is restricted to the N-terminal domain. This observation has lead to the development of a PfMSP3-based vaccine comprised solely of the highly conserved, yet poorly immunogenic, C-terminal domain. The rationale for supporting the C-terminal domain relies entirely on its conserved …

Genetic Complexity And Population Diversity Of Plasmodium Falciparum In The Peruvian Amazon, Patrick Lee Sutton

All ETDs from UAB

GENETIC COMPLEXITY AND POPULATION DIVERSITY OF PLASMODIUM FALCIPARUM IN THE PERUVIAN AMAZON PATRICK LEE SUTTON MICROBIOLOGY GRADUATE PROGRAM ABSTRACT Characterizing the genetic complexity of immunologically relevant proteins, expressed during the life cycle of P. falciparum, is essential for identifying and advancing potential vaccine candidates. The current malaria immunity paradigm is rooted in high transmission studies which have investigated the impact of high genetic diversity on the development of humoral responses. Given the dynamic nature of malaria parasites, especially their ability to acclimate to change, it is likely that regions of low transmission do not share the same malaria immunity paradigm …

Efficacy And Safety Of Intermittent Preventive Treatment With Sulfadoxine-Pyrimethamine For Malaria In African Infants: A Pooled Analysis Of Six Randomised, Placebo-Controlled Trials, J.J. Aponte, D. Schellenberg, A. Egan, A. Breckenridge, I. Carneiro, J. Critchley, I. Danquah, A. Dodoo, R. Kobbe, B. Lell, J. May, Zul Premji, S. Sanz, E. Sevene, R. Soulaymani-Becheikh, P. Winstanley, S. Adjei, S. Anemana, D. Chandramohan, S. Issifou, F. Mockenhaupt F., S. Owusu-Agyei, B. Greenwood, M.P. Grobusch, P.G. Kremsner, E. Macete, H. Mshinda, R.D. Newman, L. Slutsker, M. Tanner, P. Alonso, C. Menendez

Pathology, East Africa

Background: Intermittent preventive treatment (IPT) is a promising strategy for malaria control in infants. We undertook a pooled analysis of the safety and efficacy of IPT in infants (IPTi) with sulfadoxine-pyrimethamine in Africa. Methods: We pooled data from six double-blind, randomised, placebo-controlled trials (undertaken one each in Tanzania, Mozambique, and Gabon, and three in Ghana) that assessed the efficacy of IPTi with sulfadoxine-pyrimethamine. In all trials, IPTi or placebo was given to infants at the time of routine vaccinations delivered by WHO's Expanded Program on Immunization. Data from the trials for incidence of clinical malaria, risk of anaemia (packed-cell volume <25% or haemoglobin <80 g/L), and incidence of hospital admissions and adverse events in infants up to 12 months of age were reanalysed by use of standard outcome definitions and time periods. Analysis was by modified intention to treat, including all infants who received at least one dose of IPTi or placebo. Findings: The six trials provided data for 7930 infants (IPTi, n=3958; placebo, n=3972). IPTi had a protective efficacy of 30·3% (95% CI 19·8-39·4, p<0·0001) against clinical malaria, 21·3% (8·2-32·5, p=0·002) against the risk of anaemia, 38·1% (12·5-56·2, p=0·007) against hospital admissions associated with malaria parasitaemia, and 22·9% (10·0-34·0, p=0·001) against all-cause hospital admissions. There were 56 deaths in the IPTi group compared with 53 in the placebo group (rate ratio 1·05, 95% CI 0·72-1·54, p=0·79). One death, judged as possibly related to IPTi because it occurred 19 days after a treatment dose, was subsequently attributed to probable sepsis. Four of 676 non-fatal hospital admissions in the IPTi group were deemed related to study treatment compared with five of 860 in the placebo group. None of three serious dermatological adverse events in the IPTi group were judged related to study treatment compared with one of 13 in the placebo group. Interpretation: IPTi with sulfadoxine-pyrimethamine was safe and efficacious across a range of malaria transmission settings, suggesting that this intervention is a useful contribution to malaria control. Funding: Bill & Melinda Gates Foundation. © 2009 Elsevier Ltd. All rights reserved.

Factors Influencing Adherence To Referral Advice Following Pre-Referral Treatment With Artesunate Suppositories In Children In Rural Tanzania, Daudi Simba, Marian Warsame, Omari Kimbute, Deodatus Kakoko, Max Petzold, Goran Tomson, Zul Premji, Melba Gomes

Pathology, East Africa

Objective: WHO recommends artemisinin suppository formulations as pre-referral treatment for children who are unable to take oral medication and cannot rapidly reach a facility for parenteral treatment. We investigated factors influencing caretakers’ adherence to referral advice following pre-referral treatment of their children with rectal artesunate suppositories.

Methods: The study was nested within an intervention study that involved pre-referral treatment of all children who came to a community dispenser for treatment because they were unable to take oral medications because of repeated vomiting, lethargy, convulsions or altered consciousness. All patients who did not comply with referral advice were stratified by actions …