Malaria Research and Treatment http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Sustained Release Formulation of Primaquine for Prevention of Relapse of Plasmodium vivax Malaria: A Randomized, Double-Blind, Comparative, Multicentric Study Thu, 20 Aug 2015 14:51:25 +0000 http://www.hindawi.com/journals/mrt/2015/579864/ Background. Primaquine is used to eradicate latent Plasmodium vivax parasite from liver, with administration of standard dose daily up to 14 days. We studied efficacy, safety, and tolerability of sustained release (SR) formulation of primaquine in comparison with conventional primaquine in preventing relapse of P. vivax malaria. Methods. Microscopically confirmed cases of P. vivax malaria received chloroquine therapy for three days. Aparasitemic and asymptomatic patients were then randomized to receive either conventional primaquine 15 mg for 14 days or primaquine SR 15 mg for 14 days, or primaquine SR 30 mg for seven days. Results. Of the 360 patients, who received chloroquine therapy, 358 patients were randomized. Two-hundred eighty-eight patients completed six-month follow-up and four patients (three: conventional primaquine 15 mg (2.86%), one: primaquine SR 30 mg (0.93%)) showed relapse confirmed by PCR genotyping. Drug compliance was significantly better in primaquine SR 30 mg group (95.57%, ) without any serious adverse events. Conclusion. Primaquine SR 15 mg and primaquine SR 30 mg could be an effective alternative to conventional primaquine 15 mg due to their comparable cure rates and safety profile. Shorter treatment duration with primaquine SR 30 mg may increase patient compliance and may further reduce relapse rates. Clinical Trial Registration. This trial is registered with CTRI/2010/091/000245. Anil Pareek, Nitin Chandurkar, Nithya Gogtay, Alaka Deshpande, Arjun Kakrani, Mala Kaneria, Partha Karmakar, Arvind Jain, Dhanpat Kochar, Arun Chogle, and Arnab Ray Copyright © 2015 Anil Pareek et al. All rights reserved. Efficacy and Safety of Artesunate-Amodiaquine versus Artemether-Lumefantrine in the Treatment of Uncomplicated Plasmodium falciparum Malaria in Sentinel Sites across Côte d’Ivoire Wed, 12 Aug 2015 06:31:41 +0000 http://www.hindawi.com/journals/mrt/2015/878132/ Two years after the introduction of free Artesunate-Amodiaquine (ASAQ) and Artemether-Lumefantrine (AL) for the treatment of uncomplicated malaria in public health facilities in Côte d’Ivoire, we carried out this study to compare their efficacy and tolerability in three surveillance sites. It was a multicentre open randomised clinical trial of 3-day ASAQ treatment against AL for the treatment of 2 parallel groups of patients aged 2 years and above. The endpoints were (1) Adequate Clinical and Parasitological Response (ACPR) at day 28 and (2) the clinical and biological tolerability. Of the 300 patients who were enrolled 289, with 143 (49.5%) and 146 (50.5%) in the ASAQ and AL groups, respectively, correctly followed the WHO 2003 protocol we used. The PCR-corrected ACPR was 99.3% for each group. More than 94% of patients no longer showed signs of fever, 48 hours after treatment. Approximately 78% of the people in the ASAQ group had a parasite clearance time of 48 hours or less compared to 81% in the AL group (). Both drugs were found to be well tolerated by the patients. This study demonstrates the effectiveness and tolerability of ASAQ and AL supporting their continuous use for the treatment of uncomplicated P. falciparum malaria infection in Côte d’Ivoire. William Yavo, Abibatou Konaté, Fulgence Kondo Kassi, Vincent Djohan, Etienne Kpongbo Angora, Pulcherie Christiane Kiki-Barro, Henriette Vanga-Bosson, and Eby Ignace Hervé Menan Copyright © 2015 William Yavo et al. All rights reserved. Coagulation and Fibrinolysis Indicators and Placental Malaria Infection in an Area Characterized by Unstable Malaria Transmission in Central Sudan Thu, 30 Jul 2015 14:09:59 +0000 http://www.hindawi.com/journals/mrt/2015/369237/ This study aimed to investigate coagulation, fibrinolysis indicators, and malaria during pregnancy. Methods. A cross-sectional study was conducted at Medani, Sudan. Sociodemographic characteristics were gathered from each parturient woman (163) and malaria was investigated by blood film and placental histology. Protein C, protein S, antithrombin-III, tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor-1 levels (PAI-1) were measured using ELISA. Results. One (0.6%), three (1.8), and 19 (11.7%) of the placentae showed active, chronic, and past infection on a histopathological examination, respectively, while 140 (85.9%) of them showed no signs of malaria infection. While the mean [SD] of the protein C, antithrombin-III, and TFPI was significantly lower, there was no significant difference in protein S and PAI-1 levels in women with placental malaria infection () compared to those without placental malaria infection (140). In linear regression, placental malaria infection was associated with antithrombin-III. There was no association between placental malaria infections and protein C, protein S, TFPI, and PAI-1 levels. There was no association between hemoglobin, birth weight, and the investigated coagulation and fibrinolysis indicators. Conclusion. This study showed significantly lower levels of protein C, antithrombin-III, and TFPI in women with placental malaria infections. Amged G. Mostafa, Naser E. Bilal, Awad-Elkareem Abass, Elhassan M. Elhassan, Ahmed A. Mohmmed, and Ishag Adam Copyright © 2015 Amged G. Mostafa et al. All rights reserved. Assessment of Control Measures and Trends of Malaria in Burie-Zuria District, West Gojjam Zone, Amhara Region, North West Ethiopia Wed, 10 Jun 2015 08:08:06 +0000 http://www.hindawi.com/journals/mrt/2015/302194/ Introduction. Malaria is caused by the protozoan parasite Plasmodium and transmitted by the bite of Anopheles mosquitoes. The aim of this study was to assess control measures and trends of malaria and guide intervention measures at Burie-Zuria district, Amhara region. Methods. Descriptive cross-sectional assessment of control measures was undertaken. We used health facility records of malaria data. We surveyed households for clinical malaria cases and utilization of Long Lasting Impregnated Nets (LLINs) and its status; the condition of Indore Residual Spraying (IRS) operation at household level was observed. Results. In Zelma-Shenbekuma kebele (village) the prevalence rate of confirmed malaria cases in the 2nd week of September was 1.2 per 1000 (17) of population and increased to 11.5 per 1000 (163) of population in the 3rd week of September 2012 and reached 16.6 per 1000 (236) of population in the 1st week of November 2012. The attack rate was the highest in 1-<5 years 120.3 per 1000 (1920) of population. LLINs were distributed four years back and only five of the fifteen respondents knew about the use of LLINs and used it regularly. Four of the fifteen households were not sprayed with IRS. Conclusion. Vector control interventions were not carried out timely. Addisu Workineh Kassa, Mulugojjam Andualem Tamiru, and Addisu Gize Yeshanew Copyright © 2015 Addisu Workineh Kassa et al. All rights reserved. Malaria Parasite Density Estimated with White Blood Cells Count Reference Value Agrees with Density Estimated with Absolute in Children Less Than 5 Years in Central Ghana Tue, 07 Apr 2015 17:25:07 +0000 http://www.hindawi.com/journals/mrt/2015/923674/ Introduction. The estimation of malaria parasite density using a microscope heavily relies on White Blood Cells (WBCs) counts. An assumed WBCs count of 8000/µL has been accepted as reasonably accurate in estimating malaria parasite densities due to the challenge to accurately determine WBCs count. Method. The study used 4944 pieces of laboratory data of consented participants of age group less than 5 years. The study compared parasite densities of absolute WBCs, assumed WBCs, and the WBCs reference values in Central Ghana. Ethical approvals were given by three ethics committees. Results. The mean (±SD) WBCs and geometric mean parasite density (GMPD) were 10500/µL (±4.1) and 10644/µL (95% CI 9986/µL to 11346/µL), respectively. The difference in the GMPD compared using absolute WBCs and densities of assumed WBCs was significantly lower. The difference in GMPD obtained with an assumed WBCs count and that of the WBCs reference values for the study area, 10400/µL and 9200/µL for children in different age groups, were not significant. Discussion. Significant errors could result when assumed WBCs count is used to estimate malaria parasite density in children. GMPD generated with WBCs reference values statistically agreed with density from the absolute WBCs. When obtaining absolute WBC is not possible, the reference value can be used to estimate parasite density. Dennis Adu-Gyasi, Kwaku Poku Asante, Sam Newton, Sabastina Amoako, David Dosoo, Love Ankrah, George Adjei, Seeba Amenga-Etego, and Seth Owusu-Agyei Copyright © 2015 Dennis Adu-Gyasi et al. All rights reserved. A Pharmacokinetic Study of Antimalarial 3,5-Diaryl-2-aminopyridine Derivatives Sun, 29 Mar 2015 14:06:26 +0000 http://www.hindawi.com/journals/mrt/2015/405962/ Malaria caused by Plasmodium falciparum is responsible for approximately 80% of the incidence and 90% of deaths which occur in the World Health Organization (WHO) African region, with children and pregnant women having the highest incidence. P. falciparum has developed resistance, and therefore new effective candidate antimalarial drugs need to be developed. Previous studies identified 3,5-diaryl-2-aminopyridines as potential antimalarial drug candidates; therefore, derivatives of these compounds were synthesized in order to improve their desired properties and pharmacokinetic (PK) properties of the derivatives were investigated in a mouse model which was dosed orally and intravenously. Collected blood samples were analyzed using liquid chromatography coupled to mass spectrometer (LC-MS/MS). The mean peak plasma level of 1.9 μM was obtained at 1 hour for compound 1 and 3.3 μM at 0.5 hours for compound 2. A decline in concentration was observed with a half-life of 2.53 and 0.87 hours for compound 1 in mice dosed orally and intravenously, respectively. For compound 2 a half-life of 2.96 and 0.68 hours was recorded. The bioavailability was 69% and 59.7% for compound 1 and compound 2, respectively. Ntokozo Dambuza, Peter Smith, Alicia Evans, Dale Taylor, Kelly Chibale, and Lubbe Wiesner Copyright © 2015 Ntokozo Dambuza et al. All rights reserved. Entomological Investigations on Malaria Vectors in Some War-Torn Areas in the Trincomalee District of Sri Lanka after Settlement of 30-Year Civil Disturbance Thu, 19 Feb 2015 06:22:21 +0000 http://www.hindawi.com/journals/mrt/2015/367635/ Background. Malaria was an endemic problem in Trincomalee District, Eastern Province of Sri Lanka. Very few recent data concerning Anopheles are available which transmit malaria. Therefore, the aim of this study is to identify various Anopheles species and the dynamics of anophelines including malaria vectors in Trincomalee District for effective vector control under the current malaria elimination program embarked in the country. Method. Entomological surveys were conducted on a monthly basis, using five entomological techniques, namely, indoor hand collection (HC), window trap collection (WTC), cattle-baited net collection (CBNC), and cattle-baited hut collection (CBHC) from June 2010 to June 2012 in 32 study areas under five entomological sentinel sites. Results. Seventeen anopheline species were encountered, of which Anopheles subpictus was the predominant species in all sampling methods. It is noted that A. culicifacies and A. subpictus have adapted to breed in polluted water in urban settings which may cause serious implications on the epidemiology of malaria in the country. Conclusions. It is important to determine the abundance, biology, distribution, and relationship with climatic factors of main and secondary malaria vectors in Sri Lanka in order to initiate evidence based controlling programs under the current malaria elimination program in Sri Lanka. Nayana Gunathilaka, Menaka Hapugoda, Wimaladharma Abeyewickreme, and Rajitha Wickremasinghe Copyright © 2015 Nayana Gunathilaka et al. All rights reserved. Patient Related Factors Affecting Adherence to Antimalarial Medication in an Urban Estate in Ghana Thu, 12 Feb 2015 13:47:11 +0000 http://www.hindawi.com/journals/mrt/2015/452539/ Our aim was to measure the adherence to Artemisinin based Combination Therapy and to determine patient related factors that affect adherence. Three hundred (300) patients receiving ACT treatment dispensed from the community pharmacy were randomly selected and followed up on the fourth day after the start of their three-day therapy to assess adherence. Adherence was measured by pill count. Quantitative interviews using a semistructured questionnaire were used to assess patients’ knowledge and beliefs on malaria and its treatment. Adherence levels to the ACTs were 57.3%. Patient related factors that affected adherence to ACTs were patients’ knowledge on the dosage (; ), efficacy (; ), and side effects (; ) of the ACTs used for the management of malaria, patients’ awareness of the consequences of not completing the doses of antimalarial dispensed (; ), and patients’ belief that “natural remedies are safer than medicines” and “prescribers place too much trust in medicines.” There was no significant relationship between adherence and patients’ knowledge on the causes, signs, and symptoms of malaria. There is the need for pharmacy staff to stress on these variables when counseling patients on antimalarials as these affect adherence levels. Alexandria O. Amponsah, Helen Vosper, and Afia F. A. Marfo Copyright © 2015 Alexandria O. Amponsah et al. All rights reserved. Occurrence of pfatpase6 Single Nucleotide Polymorphisms Associated with Artemisinin Resistance among Field Isolates of Plasmodium falciparum in North-Eastern Tanzania Mon, 05 Jan 2015 13:47:07 +0000 http://www.hindawi.com/journals/mrt/2015/279028/ We aimed to determine the current prevalence of four P. falciparum candidate artemisinin resistance biomarkers L263E, E431K, A623E, and S769N in the pfatpase6 gene in a high transmission area in Tanzania in a retrospective cross sectional study using 154 archived samples collected from three previous malaria studies in 2010, 2011 and 2013. Mutations in pfatpase6 gene were detected in parasite DNA isolated from Dried Blood Spots by using PCR-RFLP. We observed overall allelic frequencies for L263E, E431K, A623E, and S769N to be 5.8% (9/154), 16.2% (25/154), 0.0% (0/154), and 3.9% (6/154). The L263E mutation was not detected in 2010 but occurred at 3.9% and 2.6% in 2011 and 2013 respectively. The L263E mutation showed a significant change of frequency between 2010 and 2011, but not between 2011 and 2013 . Frequency of E431K was highest of all without any clear trend whereas S769N increased from 2.2% in 2010 to 3.6% in 2011 and 5.1% in 2013. A623E mutation was not detected. The worrisome detection and the increase in the frequency of S769N and other mutations calls for urgent assessment of temporal changes of known artemisinin biomarkers in association with in vivo ACT efficacy. Jaffu Chilongola, Arnold Ndaro, Hipolite Tarimo, Tamara Shedrack, Sakurani Barthazary, Robert Kaaya, Alutu Masokoto, Debora Kajeguka, Reginald A. Kavishe, and John Lusingu Copyright © 2015 Jaffu Chilongola et al. All rights reserved. Evidence of Insulin Resistance in Adult Uncomplicated Malaria: Result of a Two-Year Prospective Study Tue, 23 Dec 2014 00:10:04 +0000 http://www.hindawi.com/journals/mrt/2014/136148/ The study aimed at investigating the effects of adult uncomplicated malaria on insulin resistance. Fasting levels of blood glucose (FBG), glycosylated hemoglobin (HbA1c), and serum insulin were measured in 100 diabetics and 100 age-matched controls before and during Plasmodium falciparum malaria. Insulin resistance and beta cell function were computed by homeostatic models assessment of insulin resistance (HOMAIR) and beta cell function (HOMAB) formulae, respectively. Body mass index (BMI) was computed. At baseline, diabetics had significantly higher levels of BMI, FBG, HbA1c, and HOMAIR but lower level of HOMAB than controls. Baseline insulin levels were comparable between the two study groups. During malaria, diabetics maintained significantly higher levels of BMI, FBG, and HbA1c but lower levels of insulin and HOMAB than controls. Malaria-induced HOMAIR levels were comparable between the two study groups but higher than baseline levels. Apart from BMI and HOMAB, mean levels of all the remaining parameters increased in malaria-infected controls. In malaria-infected diabetics, significant increase was only observed for insulin and HOMAIR but not the other measured parameters. Uncomplicated malaria increased insulin resistance in diabetics and controls independent of BMI. This finding may have implications for the evolution of T2DM in malaria-endemic regions. Samuel Acquah, Johnson Nyarko Boampong, Benjamin Ackon Eghan Jnr, and Magdalena Eriksson Copyright © 2014 Samuel Acquah et al. All rights reserved. Bioinformatic Identification of Peptidomimetic-Based Inhibitors against Plasmodium falciparum Antigen AMA1 Thu, 18 Dec 2014 00:10:17 +0000 http://www.hindawi.com/journals/mrt/2014/642391/ Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a valuable vaccine candidate and exported on the merozoite surface at the time of erythrocyte invasion. PfAMA1 interacts with rhoptry neck protein PfRON2, a component of the rhoptry protein complex, which forms the tight junction at the time of invasion. Phage display studies have identified a 15-residue (F1) and a 20-residue (R1) peptide that bind to PfAMA1 and block the invasion of erythrocytes. Cocrystal structures of central region of PfAMA1 containing disulfide-linked clusters (domains I and II) with R1 peptide and a peptide derived from PfRON2 showed strong structural similarity in binding. The peptides bound to a hydrophobic groove surrounded by domain I and II loops. In this study, peptidomimetics based on the crucial PfAMA1-binding residues of PfRON2 peptide have been identified. Top 5 peptidomimetics when checked for their docking on the region of PfAMA1 encompassing the hydrophobic groove were found to dock on the groove. Drug-like molecules having structural similarity to the top 5 peptidomimetics were identified based on their binding ability to PfAMA1 hydrophobic groove in blind docking. These inhibitors provide potential lead compounds, which could be used in the development of antimalarials targeting PfAMA1. Asrar Alam Copyright © 2014 Asrar Alam. All rights reserved. Exploiting Unique Structural and Functional Properties of Malarial Glycolytic Enzymes for Antimalarial Drug Development Wed, 17 Dec 2014 00:00:00 +0000 http://www.hindawi.com/journals/mrt/2014/451065/ Metabolic enzymes have been known to carry out a variety of functions besides their normal housekeeping roles known as “moonlighting functions.” These functionalities arise from structural changes induced by posttranslational modifications and/or binding of interacting proteins. Glycolysis is the sole source of energy generation for malaria parasite Plasmodium falciparum, hence a potential pathway for therapeutic intervention. Crystal structures of several P. falciparum glycolytic enzymes have been solved, revealing that they exhibit unique structural differences from the respective host enzymes, which could be exploited for their selective targeting. In addition, these enzymes carry out many parasite-specific functions, which could be of potential interest to control parasite development and transmission. This review focuses on the moonlighting functions of P. falciparum glycolytic enzymes and unique structural differences and functional features of the parasite enzymes, which could be exploited for therapeutic and transmission blocking interventions against malaria. Asrar Alam, Md. Kausar Neyaz, and Syed Ikramul Hasan Copyright © 2014 Asrar Alam et al. All rights reserved. Sociodemographic Determinants of Malaria among Under-Five Children in Ghana Sun, 14 Dec 2014 06:47:59 +0000 http://www.hindawi.com/journals/mrt/2014/304361/ Background. Malaria is an entrenched global health challenge particularly in the sub-Saharan African countries. However, in Ghana, little is known about the determinants of malaria prevalence among under-five children. As such, this study sought to examine the sociodemographic factors that determine malaria among under-five children in Ghana. Methods. This paper used secondary data drawn from the 2008 Ghana Demographic and Health Survey. Bivariate analysis and complementary log-log regression models were used to examine the determinants of malaria prevalence among under-five children in Ghana for the study period. Results. The results therefore revealed that region of residence, age of child, and ownership of mosquito net were the key predictors of malaria cases among under-five children in Ghana for the five-year period preceding the survey. Conclusion. It is therefore imperative that special education on prevention of malaria should be intensified by the National Malaria Control Programme in all the regions in order to reduce malaria prevalence particularly among under-five children in Ghana. Samuel Harrenson Nyarko and Anastasia Cobblah Copyright © 2014 Samuel Harrenson Nyarko and Anastasia Cobblah. All rights reserved. Imported Malaria in Portugal 2000–2009: A Role for Hospital Statistics for Better Estimates and Surveillance Sun, 07 Dec 2014 08:34:32 +0000 http://www.hindawi.com/journals/mrt/2014/373029/ Background. Although eradicated in Portugal, malaria keeps taking its toll on travelers and migrants from endemic countries. Disease notification is mandatory but is compromised by underreporting. Methods. A retrospective study on malaria hospitalizations for 10 consecutive years (2000–2009) was conducted. Data on hospitalizations and notifications were obtained from Central Administration of Health System and Health Protection Agency, respectively. For data selection ICD-9 CM and ICD-10 were used: codes 084*, 647.4, and B50–B54. Variables were gender, age, agent and origin of infection, length of stay (LOS), lethality, and comorbidities. Analysis included description, hypothesis testing, and regression. Results. There were 2003 malaria hospitalizations and 480 notified hospitalized cases, mainly in young male adults. P. falciparum was the main agent of infection acquired mainly in sub-Saharan Africa. Lethality was 1.95% and mean LOS was 8.09 days. Older age entailed longer LOS and increased lethality. Discussion. From 2000 to 2009, there were 2003 malaria hospitalizations with decreasing annual incidence, these numbers being remarkably higher than those notified. The national database of diagnosis related groups, reflecting hospitalizations on NHS hospitals, may be an unexplored complementary source for better estimates on imported malaria. Ana Glória Fonseca, Sara S. Dias, João Luis Baptista, and Jorge Torgal Copyright © 2014 Ana Glória Fonseca et al. All rights reserved. Mother-to-Children Plasmodium falciparum Asymptomatic Malaria Transmission at Saint Camille Medical Centre in Ouagadougou, Burkina Faso Sun, 23 Nov 2014 12:21:43 +0000 http://www.hindawi.com/journals/mrt/2014/390513/ Background. Malaria’s prevalence during pregnancy varies widely in parts of sub-Saharan Africa, including Burkina Faso. The objective of this study was to evaluate the incidence of mother-to-child malaria transmission during childbirth at St. Camille Medical Centre in the city of Ouagadougou. Methods. Two hundred and thirty-eight (238) women and their newborns were included in the study. Women consenting to participate in this study responded to a questionnaire that identified their demographic characteristics. Asymptomatic malaria infection was assessed by rapid detection test Acon (Acon Malaria Pf, San Diego, USA) and by microscopic examination of Giemsa-stained thick and thin smears from peripheral, placental, and umbilical cord blood. Birth weights were recorded and the biological analyses of mothers and newborns’ blood were also performed. Results. The utilization of long-lasting insecticidal nets (LLINs) and intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) were 86.6% and 84.4%, respectively. The parasitic infection rates of 9.5%, 8.9%, and 2.8% were recorded, respectively, for the peripheral, placental, and umbilical cord blood. Placental infection was strongly associated with the presence of parasites in the maternal peripheral blood and a parasite density of >1000 parasites/µL. Conclusion. The prevalence of congenital malaria was reduced but was associated with a high rate of mother-to-child malaria transmission. Zoenabo Douamba, Nangnéré Ginette Laure Dao, Théodora Mahoukédé Zohoncon, Cyrille Bisseye, Tegwindé Rebeca Compaoré, Jacques Gilbert Kafando, Bavouma Charles Sombie, Djeneba Ouermi, Florencia W. Djigma, Paul Ouedraogo, Nadine Ghilat, Virginio Pietra, Vittorio Colizzi, and Jacques Simpore Copyright © 2014 Zoenabo Douamba et al. All rights reserved. Low Prevalence of Pfcrt Resistance Alleles among Patients with Uncomplicated Falciparum Malaria in Niger Six Years after Chloroquine Withdrawal Sun, 23 Nov 2014 08:18:10 +0000 http://www.hindawi.com/journals/mrt/2014/614190/ Chloroquine (CQ) resistance is widespread in Africa, but few data are available for Niger. Pfcrt haplotypes (aa 56–118) and ex vivo responses to CQ and amodiaquine were characterized for 26 isolates collected in South Niger from children under 15 years of age suffering from uncomplicated falciparum malaria, six years after the introduction of artemisinin-based combinations and the withdrawal of CQ. The wild-type Pfcrt haplotype CVMNK was found in 22 of the 26 isolates, with CVIET sequences observed in only three of the samples. We also describe for the first time a new CVINT haplotype. The ex vivo responses were better for CVMNK than for CVIET parasites. Pfcrt sequence data were compared with those obtained for 26 additional parasitized blood samples collected in Gabon, from an area of CQ resistance used as a control. Our findings suggest that there has been a significant decline in CQ-resistant genotypes since the previous estimates for Niger were obtained. No such decline in molecular resistance to CQ was observed in the subset of samples collected in similar conditions from Gabon. These results have important implications for public health and support the policy implemented in Niger since 2005, which aims to increase the efficacy and availability of antimalarial drugs whilst controlling the spread of resistance. Adamou Salissou, Halima Zamanka, Brigitte Biyghe Binze, Taiana Rivière, Magalie Tichit, Maman Laminou Ibrahim, and Thierry Fandeur Copyright © 2014 Adamou Salissou et al. All rights reserved. Molecular Detection of Plasmodium falciparum Infection in Matched Peripheral and Placental Blood Samples from Delivering Women in Libreville, Gabon Mon, 17 Nov 2014 11:35:05 +0000 http://www.hindawi.com/journals/mrt/2014/486042/ Submicroscopic infections account for more than 50% of all Plasmodium (P.) infections in areas with decreasing malaria prevalence and might contribute to poor pregnancy outcomes. The frequency of submicroscopic P. falciparum infections was assessed in matched peripheral and placental blood samples with microscopy negative or discordant results according to IPTp administration. Methods. P. falciparum infection was detected by nested PCR in matched blood samples collected from delivering women with a history of antimalarial drug treatment and living in Gabon. Results. Submicroscopic P. falciparum infections were detected in 87% () of the 44 selected matched samples. Plasmodial DNA was found in 90% () and 87% () of microscopy negative peripheral and placental blood samples, respectively. Overall, 95% of samples obtained during the high IPTp-SP coverage period had a submicroscopic infection versus 79% among those from the low coverage period. Conclusion. Submicroscopic infections frequency is high in peripheral and placental blood samples from delivering women with a history of antimalarial treatment whatever the level of IPTp coverage. These data highlight the need of accurate diagnostic tools for a regular antenatal screening of malaria during the pregnancy in endemic areas. Marie L. Tshibola Mbuyi, Marielle K. Bouyou-Akotet, and Denise P. Mawili-Mboumba Copyright © 2014 Marie L. Tshibola Mbuyi et al. All rights reserved. Role of Different Pfcrt and Pfmdr-1 Mutations in Conferring Resistance to Antimalaria Drugs in Plasmodium falciparum Tue, 11 Nov 2014 06:04:38 +0000 http://www.hindawi.com/journals/mrt/2014/950424/ Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malaria in endemic areas. Antimalaria drugs act on different intracellular targets. The majority of them interfere with digestive vacuoles (DVs) while others affect other organelles, namely, apicoplast and mitochondria. Prevention of drug accumulation or access into the target site is one of the mechanisms that plasmodium adopts to develop resistance. Plasmodia are endowed with series of transporters that shuffle drugs away from the target site, namely, pfmdr (Plasmodium falciparum multidrug resistance transporter) and pfcrt (Plasmodium falciparum chloroquine resistance transporter) which exist in DV membrane and are considered as putative markers of CQ resistance. They are homologues to human P-glycoproteins (P-gh or multidrug resistance system) and members of drug metabolite transporter (DMT) family, respectively. The former mediates drifting of xenobiotics towards the DV while the latter chucks them outside. Resistance to drugs whose target site of action is intravacuolar develops when the transporters expel them outside the DVs and vice versa for those whose target is extravacuolar. In this review, we are going to summarize the possible pfcrt and pfmdr mutation and their role in changing plasmodium sensitivity to different anti-Plasmodium drugs. Zaid O. Ibraheem, R. Abd Majid, S. Mohd. Noor, H. Mohd. Sedik, and R. Basir Copyright © 2014 Zaid O. Ibraheem et al. All rights reserved. Clinical Profile of Plasmodium vivax Malaria in Children and Study of Severity Parameters in relation to Mortality: A Tertiary Care Centre Perspective in Mumbai, India Sun, 02 Nov 2014 07:59:30 +0000 http://www.hindawi.com/journals/mrt/2014/765657/ Background. While research on P. vivax is scarce because it is considered benign, it has become evident with implementation of molecular diagnosis that it can also cause multiple organ dysfunction and severe life-threatening disease. Objective. To study clinical presentations and complications of P. vivax malaria and mortality correlation to severity parameters as defined by WHO criteria for severe malaria. Materials and methods. This study was conducted in a tertiary care centre in Mumbai. Confirmed P. vivax cases were enrolled and studied for their clinical profile, and WHO severity parameters were tested for their frequency and association to mortality. Result. The most common presentation was fever followed by pallor. 26% of the cases satisfied one or more criteria of WHO severity parameters. 2 cases died; both had pulmonary edema and bleeding. The major predictor of mortality among these predefined severity criteria was pulmonary edema/ARDS. Patients with severe anemia, circulatory collapse, and repeated generalized convulsion had 100% survival rate. Leukopenia was present in 10% of the cases. Both cases with mortality had leukopenia. Conclusion. P. vivax monoinfection tends to have severe complications in children. There is a need to review severity criteria for P. vivax malaria. Manju Kumari and Radha Ghildiyal Copyright © 2014 Manju Kumari and Radha Ghildiyal. All rights reserved. Evaluation of the Quality of Artemisinin-Based Antimalarial Medicines Distributed in Ghana and Togo Mon, 27 Oct 2014 07:09:46 +0000 http://www.hindawi.com/journals/mrt/2014/806416/ This study, conducted as part of our overall goal of regular pharmacovigilance of antimalarial medicines, reports on the quality of 132 artemisinin-based antimalarial medicines distributed in Ghana and Togo. Three methods were employed in the quality evaluation—basic (colorimetric) tests for establishing the identity of the requisite active pharmaceutical ingredients (APIs), semi-quantitative TLC assay for the identification and estimation of API content, and HPLC assay for a more accurate quantification of API content. From the basic tests, only one sample totally lacked API. The HPLC assay, however, showed that 83.7% of the ACTs and 57.9% of the artemisinin-based monotherapies failed to comply with international pharmacopoeia requirements due to insufficient API content. In most of the ACTs, the artemisinin component was usually the insufficient API. Generally, there was a good correlation between the HPLC and SQ-TLC assays. The overall failure rates for both locally manufactured (77.3%) and imported medicines (77.5%) were comparable. Similarly the unregistered medicines recorded a slightly higher overall failure rate (84.7%) than registered medicines (70.8%). Only two instances of possible cross-border exchange of medicines were observed and there was little difference between the medicine quality of collections from border towns and those from inland parts of both countries. Dorcas Osei-Safo, Amegnona Agbonon, Daniel Yeboah Konadu, Jerry Joe Ebow Kingsley Harrison, Mamadou Edoh, Andrew Gordon, Messanvi Gbeassor, and Ivan Addae-Mensah Copyright © 2014 Dorcas Osei-Safo et al. All rights reserved. Time Course of the Changes in Novel Trioxane Antimalarial 99/411 Pharmacokinetics upon Antiepileptic Drugs Co-Administration in SD Rats Tue, 14 Oct 2014 09:15:57 +0000 http://www.hindawi.com/journals/mrt/2014/756965/ Objective. The study aimed to evaluate the influences of coadministration of antiepileptic drugs (AEDs) on an antimalarial candidate 99/411 pharmacokinetic (PK) profile. Method. For this, single oral dose PK drug interaction studies were conducted between 99/411 and FDA approved AEDs, namely, Phenytoin (PHT), Carbamazepine (CBZ), and Gabapentin (GB) in both male and female SD rats, to assess the coadministered and intersexual influences on 99/411 PK profile. Results. Studies revealed that there were no significant alterations in the PK profile of 99/411 upon PHT and CBZ coadministration in both male and female rats, while systemic exposure of 99/411 was significantly increased by about 80% in female rats upon GB coadministration. In terms of AUC, there was an increase from 2471 ± 586 to 4560 ± 1396 ng·h/mL. Overall, it was concluded that simultaneous administration of AEDs with 99/411 excludes the requirements for dose adjustment, additional therapeutic monitoring, contraindication to concomitant use, and/or other measures to mitigate risk, except for GB coadministration in females. These findings are further helpful to predict such interactions in humans, when potentially applied through proper allometric scaling to extrapolate the data. Yeshwant Singh, Hari Narayan Kushwaha, Anamika Misra, Mahendra Kumar Hidau, and Shio Kumar Singh Copyright © 2014 Yeshwant Singh et al. All rights reserved. Pharmacovigilance Practices for Better Healthcare Delivery: Knowledge and Attitude Study in the National Malaria Control Programme of India Mon, 15 Sep 2014 06:37:22 +0000 http://www.hindawi.com/journals/mrt/2014/837427/ Objective. With large scale rollout of artemisinin based therapy in the National Malaria Control Programme of India, a risk management plan is needed. This depends on adverse drug reaction (ADR) reporting by the healthcare professionals (HCPs). For the programme to be successful, an understanding of the mindset of HCPs is critical. Hence, the present study was designed to assess and compare the ADR reporting beliefs of HCPs involved in the National Malaria Control Programme of India. Methods. A cross–sectional survey was conducted amongst the HCPs who manage malaria up to the district level in India. A 5-point Likert scale-based questionnaire was developed as a study tool. Results. A total of 154 HCPs participated in the study (age: 42.4 ± 10.1 years with 33.8% being females). About 61% felt that only medically qualified HCPs are responsible for ADR reporting. Likeliness to report in future was mentioned by 45% HCPs. The knowledge score was relatively lower for life science graduates (). Knowledge correlated positively with attitude (; ). Conclusion. Based on the caveats identified, a specific and targeted in-service education with hands-on training on ADR monitoring and reporting needs to be designed to boost real time pharmacovigilance in India. Pooja Gupta, Anupkumar R. Anvikar, Neena Valecha, and Yogendra K. Gupta Copyright © 2014 Pooja Gupta et al. All rights reserved. Pharmacokinetic Study and Bioavailability of a Novel Synthetic Trioxane Antimalarial Compound 97/63 in Rats Thu, 11 Sep 2014 09:23:14 +0000 http://www.hindawi.com/journals/mrt/2014/759392/ Single dose pharmacokinetics study of 97/63 (IND191710, 2004), a trioxane antimalarial developed by Central Drug Research Institute, Lucknow, India, was studied in rats following intravenous and oral administration. Serum samples were analysed by HPLC-UV assay. Separation was achieved on a RP-18 column attached with a guard using acetonitrile : phosphate buffer (70 : 30% v/v) with UV detector at wavelength 244 nm. Serum samples were extracted with n-hexane. Two-compartment model without lag time and first-order elimination rate was considered to be the best fit to explain the generated oral and intravenous data. Method was sensitive with limit of quantification of 10 ng mL−1. Recovery was 74%. Terminal half-life and area under curve (AUC) after administering single oral (72 mg kg−1) and intravenous (18 mg kg−1) doses were 10.61 h, 10.57 h, and 1268.97 ng h mL−1, 2025.75 ng h mL−1, respectively. After oral dose, 97/63 was rapidly absorbed attaining maximum concentration 229.24 ng mL−1 at 1 h. Bioavailability of 97/63 was 16%. The lower bioavailability of drug may be due to poor solubility and first-pass metabolism and can be improved by prodrug formation of 97/63. Hari Narayan Kushwaha, Neel Kamal Mohan, Ashok Kumar Sharma, and Shio Kumar Singh Copyright © 2014 Hari Narayan Kushwaha et al. All rights reserved. Antirelapse Efficacy of Various Primaquine Regimens for Plasmodium vivax Wed, 10 Sep 2014 05:57:36 +0000 http://www.hindawi.com/journals/mrt/2014/347018/ Background. Efficacy of standard dose of primaquine (PQ) as antirelapse for P. vivax has decreased. We aimed to assess efficacy of different PQ regimens. Methods. It was an open label, randomized, controlled, parallel group, assessor blind study comparing antirelapse efficacy of 3 PQ regimens ( mg/day × 14 days,  mg/day × 7 days, and  mg/day × 14 days) with no PQ group (A) in P. vivax patients. Paired primary and recurrence samples were subjected to 3 methods: (i) month of recurrence and genotyping, (ii) by PCR-RFLP, and (iii) PCR sequencing, to differentiate relapse and reinfection. The rates of recurrence relapse and reinfection were compared. Methods were compared for concordance between them. Results. The recurrence rate was 16.39%, 8.07%, 10.07%, and 6.62% in groups A, B, C, and D, respectively . The relapse rate was 6.89%, 1.55%, 4%, and 3.85% as per the month of recurrence; 8.2%, 2%, 4.58%, and 3.68% as per PCR-RFLP; and 2.73%, 1.47%, 1.55%, and 1.53% as per PCR sequencing for groups A, B, C, and D, respectively. The concordance between methods was low, 45%. Conclusion. The higher recurrence rate in no PQ as compared to PQ groups documents PQ antirelapse activity. Regimens tested were safe. However, probable resistance to PQ warrants continuous monitoring and low concordance and limitations in the methods warrant caution in interpreting. D. D. Rajgor, N. J. Gogtay, V. S. Kadam, M. M. Kocharekar, M. S. Parulekar, S. S. Dalvi, A. B. Vaidya, and N. A. Kshirsagar Copyright © 2014 D. D. Rajgor et al. All rights reserved. Forecasting Malaria Cases Using Climatic Factors in Delhi, India: A Time Series Analysis Wed, 23 Jul 2014 11:52:35 +0000 http://www.hindawi.com/journals/mrt/2014/482851/ Background. Malaria still remains a public health problem in developing countries and changing environmental and climatic factors pose the biggest challenge in fighting against the scourge of malaria. Therefore, the study was designed to forecast malaria cases using climatic factors as predictors in Delhi, India. Methods. The total number of monthly cases of malaria slide positives occurring from January 2006 to December 2013 was taken from the register maintained at the malaria clinic at Rural Health Training Centre (RHTC), Najafgarh, Delhi. Climatic data of monthly mean rainfall, relative humidity, and mean maximum temperature were taken from Regional Meteorological Centre, Delhi. Expert modeler of SPSS ver. 21 was used for analyzing the time series data. Results. Autoregressive integrated moving average, ARIMA (0,1,1) (0,1,0)12, was the best fit model and it could explain 72.5% variability in the time series data. Rainfall (P value = 0.004) and relative humidity (P value = 0.001) were found to be significant predictors for malaria transmission in the study area. Seasonal adjusted factor (SAF) for malaria cases shows peak during the months of August and September. Conclusion. ARIMA models of time series analysis is a simple and reliable tool for producing reliable forecasts for malaria in Delhi, India. Varun Kumar, Abha Mangal, Sanjeet Panesar, Geeta Yadav, Richa Talwar, Deepak Raut, and Saudan Singh Copyright © 2014 Varun Kumar et al. All rights reserved. Retracted: A Study on Course of Infection and Haematological Changes in falciparum-Infected in Comparison with Artemisinin(s)-Treated Mice Thu, 03 Jul 2014 11:42:07 +0000 http://www.hindawi.com/journals/mrt/2014/845487/ Malaria Research and Treatment Copyright © 2014 Malaria Research and Treatment. All rights reserved. Does the Use of Dihydroartemisinin-Piperaquine in Treating Patients with Uncomplicated falciparum Malaria Reduce the Risk for Recurrent New falciparum Infection More Than Artemether-Lumefantrine? Thu, 19 Jun 2014 11:00:08 +0000 http://www.hindawi.com/journals/mrt/2014/263674/ Malaria contributes significantly to the global disease burden. The World Health Organization recommended the use of artemisinin-based combination therapies (ACTs) for treatment of uncomplicated falciparum malaria a decade ago in response to problems of drug resistance. This review compared two of the ACTs—Dihydroartemisinin-Piperaquine (DP) and Artemether-Lumefantrine (AL) to provide evidence which one has the ability to offer superior posttreatment prophylaxis at 28 and 42 days posttreatment. Four databases (MEDLINE, EMBASE, Cochrane Database and Global Health) were searched on June 2, 2013 and a total of seven randomized controlled trials conducted in sub-Sahara Africa were included. Results involving 2, 340 participants indicates that reduction in risk for recurrent new falciparum infections (RNIs) was 79% at day 28 in favour of DP [RR, 0.21; 95% CI: 0.14 to 0.32, ], and at day 42 was 44% favouring DP [RR, 0.56; 95% CI: 0.34 to 0.90; ]. No significant difference was seen in treatment failure rates between the two drugs at days 28 and 42. It is concluded that use of DP offers superior posttreatment prophylaxis compared to AL in the study areas. Hence DP can help reduce malaria cases in such areas more than AL. Wisdom Akpaloo and Edward Purssell Copyright © 2014 Wisdom Akpaloo and Edward Purssell. All rights reserved. Comparison of Clinical Profile between P. vivax and P. falciparum Malaria in Children: A Tertiary Care Centre Perspective from India Wed, 09 Apr 2014 08:59:14 +0000 http://www.hindawi.com/journals/mrt/2014/132672/ Background. Malaria is a one of the leading causes of morbidity and mortality in tropical countries. Plasmodium vivax (P. vivax) is usually thought to be causing benign malaria with low incidence of complications as compared to Plasmodium falciparum (P. falciparum). Methods. This retrospective observational study included malaria patients who were admitted to K.T. Children Hospital and P.D.U. Government Medical College, Rajkot, a tertiary care teaching hospital, Gujarat, western India, during the period January 2012 to December 2012. Inclusion criteria were patients in whom either P. falciparum or P. vivax was positive on rapid malaria antigen test and peripheral blood smear. Patients showing mixed infections were excluded from study. Results. A total of 79 subjects (mean age years) were included in the study. It consisted of 47 P. vivax and 32 P. falciparum cases. The P. vivax cases consisted of 33 (70.2%) males and 11 (19.8%) females while P. falciparum cases consisted of 14 (43.8%) males and 18 (56.2%) females. One patient of each P. vivax and P. falciparum expired. There was no statistical significant difference found between complications such as anemia, thrombocytopenia, liver and renal dysfunction, ARDS, and cerebral malaria between P. vivax and P. falciparum. Conclusion. We conclude that P. vivax monoinfection tends to have as similar course and complications as compared to malaria due to P. falciparum monoinfection. Jagdish Prasad Goyal and Aarti M. Makwana Copyright © 2014 Jagdish Prasad Goyal and Aarti M. Makwana. All rights reserved. Single Ascending Dose Safety and Pharmacokinetics of CDRI-97/78: First-in-Human Study of a Novel Antimalarial Drug Thu, 27 Mar 2014 09:38:29 +0000 http://www.hindawi.com/journals/mrt/2014/372521/ Background. CDRI 97/78 has shown efficacy in animal models of falciparum malaria. The present study is the first in-human phase I trial in healthy volunteers. Methods. The study was conducted in 50 healthy volunteers in a single, ascending dose, randomized, placebo-controlled, double blind design. The dose ranges evaluated were from 80 mg to 700 mg. Volunteers were assessed for clinical, biochemical, haematological, radiographic, and electrocardiographic parameters for any adverse events in an in-house facility. After evaluation of safety study results, another cohort of 16 participants were administered a single oral dose of 200 mg of the drug and a detailed pharmacokinetic analysis was undertaken. Results. The compound was found to be well tolerated. MTD was not reached. The few adverse events noted were of grade 2 severity, not requiring intervention and not showing any dose response relationship. The laboratory and electrocardiographic parameters showed statistically significant differences, but all were within the predefined normal range. These parameters were not associated with symptoms/signs and hence regarded as clinically irrelevant. Mean values of , MRT, and of the active metabolite 97/63 were  h,  h, and  ng·h/mL, respectively Conclusion. The novel 1,2,4 trioxane CDRI 97/78 is safe and will be an asset in malarial therapy if results are replicated in multiple dose studies and benefit is shown in confirmatory trials. N. Shafiq, S. Rajagopalan, H. N. Kushwaha, N. Mittal, N. Chandurkar, A. Bhalla, S. Kaur, P. Pandhi, G. D. Puri, S. Achuthan, A. Pareek, S. K. Singh, J. S. Srivastava, S. P. S. Gaur, and S. Malhotra Copyright © 2014 N. Shafiq et al. All rights reserved. The Effect of Mass Media Campaign on the Use of Insecticide-Treated Bed Nets among Pregnant Women in Nigeria Thu, 20 Mar 2014 07:16:30 +0000 http://www.hindawi.com/journals/mrt/2014/694863/ Background. Malaria during pregnancy is a major public health problem in Nigeria especially in malaria-endemic areas. It increases the risk of low birth weight and child/maternal morbidity/mortality. This paper addresses the impact of radio campaigns on the use of insecticide-treated bed nets among pregnant women in Nigeria. Methods. A total of 2,348 pregnant women were interviewed during the survey across 21 of Nigeria’s 36 states. Respondents were selected through a multistage sampling technique. Analysis was based on multivariate logistic regression. Results. Respondents who knew that sleeping under ITN prevents malaria were 3.2 times more likely to sleep under net (OR: 3.15; 95% CI: 2.28 to 4.33; ). Those who listened to radio are also about 1.6 times more likely to use ITN (OR: 1.56; 95% CI: 1.07 to 2.28; ), while respondents who had heard of a specific sponsored radio campaign on ITN are 1.53 times more likely to use a bed net (). Conclusion. Pregnant women who listened to mass media campaigns were more likely to adopt strategies to protect themselves from malaria. Therefore, behavior change communication messages that are aimed at promoting net use and antenatal attendance are necessary in combating malaria. A. Ankomah, S. B. Adebayo, E. D. Arogundade, J. Anyanti, E. Nwokolo, U. Inyang, Oladipupo B. Ipadeola, and M. Meremiku Copyright © 2014 A. Ankomah et al. All rights reserved.