Malaria Research and Treatment The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . 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 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 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 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 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 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 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 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 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 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 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. Assessment of Risk Factors Associated with Malaria Transmission in Tubu Village, Northern Botswana Sun, 16 Mar 2014 13:49:30 +0000 This study investigated potential risk factors associated with malaria transmission in Tubu village, Okavango subdistrict, a malaria endemic area in northern Botswana. Data was derived from a census questionnaire survey, participatory rural appraisal workshop, field observations, and mosquito surveys. History of malaria episodes was associated with several factors: household income (), late outdoor activities (OR = 7.016; CI = 1.786–27.559), time spent outdoors (), travel outside study area (OR = 2.70; CI = 1.004–7.260), nonpossession of insecticide treated nets (OR = 0.892; CI = 0.797–0.998), hut/house structure (OR = 11.781; CI = 3.868–35.885), and homestead location from water bodies (). No associations were established between history of malaria episodes and the following factors: being a farmer () and number of nets possessed (). Eave size was not associated with mosquito bites (), frequency of mosquito bites (), and time of mosquito bites (). Possession of nets was very high (94.7%). Close proximity of a health facility and low vegetation cover were added advantages. Some of the identified risk factors are important for developing effective control and elimination strategies involving the community, with limited resources. Elijah Chirebvu, Moses John Chimbari, and Barbara Ntombi Ngwenya Copyright © 2014 Elijah Chirebvu et al. All rights reserved. Effect of Iron/Folic Acid Supplementation on the Outcome of Malaria Episodes Treated with Sulfadoxine-Pyrimethamine Sun, 19 Jan 2014 00:00:00 +0000 Folic acid supplementation may potentially alter the efficacy of sulfadoxine-pyrimethamine (SP) treatment in children with malaria. However, there is lack of evidence from randomized controlled trials and effects of folic acid supplementation on clinical efficacy of SP therapy remain moderately understood among children. In a double masked, placebo-controlled trial among preschool children in Pemba Island (Tanzania), iron and folic acid supplementation (Fe/FA) showed an increased risk of hospitalizations and death. In the present paper, we evaluated if folic acid supplementation reduced the efficacy of malaria treatment and thereby contributed to observed adverse effects. During the study, 1648 children had confirmed malarial episodes and received either sulphadoxine-pyrimethamine (SP) treatment and iron folic acid or SP treatment and placebo. These children were evaluated for recovery and incidence of hospitalization during the next 15, 30, and 140 days. Two groups did not differ in malarial episode or hospitalization rate on subsequent 15, 30, and 140 days. Altered efficacy of SP by folic acid was not observed and did not contribute to adverse events in the previous trial. This trial is registered with ISRCTN59549825. Sunil Sazawal, Robert E. Black, Ibrahim Kabole, Arup Dutta, Usha Dhingra, and Mahdi Ramsan Copyright © 2014 Sunil Sazawal et al. All rights reserved. Awareness and Utilization of Affordable Medicine Facility-Malaria among Caregivers of Under-Five Children in Ibadan North-West Local Government Area, Oyo State Mon, 30 Dec 2013 14:51:53 +0000 Introduction. Distribution of Affordable Medicine Facility-malaria Artemisinin Combination Therapies (AMFm-ACTs) started in Nigeria in 2011, but its use at community level has not been documented. Methods. Four hundred seventy-eight caregivers whose under-five children had fever within two weeks prior to the survey were selected using cluster sampling technique. Information on sociodemographic characteristics, treatment seeking for malaria, and awareness and use of AMFm-ACTs was collected using an interviewer administered questionnaire. Result. More than half of the respondents (51.2%) bought AMFm-ACTs without prescription. Awareness of AMFm was low as only 9.1% has heard about the programme. Overall, 29.2% used AMFm-ACTs as their first line choice of antimalarial drug. On bivariate analysis age, group (25–34 years), public servants, respondents with tertiary education, respondents with high socioeconomic status, respondents with poor knowledge of symptoms of malaria, awareness of AMFm-ACTs, availability of AMFm-ACTs, and sources of drug were significantly associated with utilization of AMFm-ACTs (). Logistic regression demonstrated that only people who were aware of AMFM-ACTs predicted its use (AOR: 0.073; CI: 0.032–0.166; ). Conclusion. Interventions which targeted at raising awareness of AMFm-ACTs among people at risk of malaria are advocated for implementation. Ikeoluwapo O. Ajayi, Tolulope Soyannwo, and Onoja M. Akpa Copyright © 2013 Ikeoluwapo O. Ajayi et al. All rights reserved. Clinical Manifestations, Treatment, and Outcome of Hospitalized Patients with Plasmodium vivax Malaria in Two Indian States: A Retrospective Study Sun, 29 Dec 2013 18:29:39 +0000 This was a retrospective study done on 110 patients hospitalized with P. vivax malaria in three medical college hospitals, one in the union territory of Chandigarh and the other two in Gujarat, that is, Ahmedabad and Surat. The clinical presentation, treatment, and outcome were recorded. As per WHO criteria for severity, 19 of 110 patients had severe disease—six patients had clinical jaundice with hepatic dysfunction, three patients had severe anemia, three had spontaneous bleeding, two had acute respiratory distress syndrome, and one had cerebral malaria, hyperparasitemia, renal failure, circulatory collapse, and metabolic acidosis. All patients with severe P. vivax malaria survived, but one child with cerebral malaria had neurological sequelae. There was wide variation in the antimalarial treatment received at the three centres. Plasmodium vivax malaria can no longer be considered a benign condition. WHO guidelines for treatment of P. vivax malaria need to be reinforced. Jagjit Singh, Bhargav Purohit, Anupama Desai, Lalita Savardekar, Preeti Shanbag, and Nilima Kshirsagar Copyright © 2013 Jagjit Singh et al. All rights reserved. Prevalence of Malaria from Blood Smears Examination: A Seven-Year Retrospective Study from Metema Hospital, Northwest Ethiopia Mon, 16 Dec 2013 08:50:35 +0000 Background. Malaria is a major public health problem in Ethiopia where an estimated 68% of the population lives in malarious areas. Studying its prevalence is necessary to implement effective control measures. Therefore, the aim of this study was to determine seven-year slide positive rate of malaria. Methods. A retrospective study was conducted at Metema Hospital from September 2006 to August 2012. Seven-year malaria cases data had been collected from laboratory registration book. Results. A total of 55,833 patients were examined for malaria; of these, 9486 (17%) study subjects were positive for malaria. The predominant Plasmodium species detected was P. falciparum (8602) (90.7%) followed by P. vivax (852) (9%). A slide positive rate of malaria within the last seven years (2006–2012) was almost constant with slight fluctuation. The age groups of 5–14 years old were highly affected by malariainfection (1375) (20.1%), followed by 15–29 years old (3986) (18.5%). High slide positive rate of malaria occurred during spring (September–November), followed by summer (June–August). Conclusion. Slide positive rate of malaria was high in study area. Therefore, health planners and administrators should give intensive health education for the community. Getachew Ferede, Abiyu Worku, Alemtegna Getaneh, Ali Ahmed, Tarekegn Haile, Yenus Abdu, Belay Tessema, Yitayih Wondimeneh, and Abebe Alemu Copyright © 2013 Getachew Ferede et al. All rights reserved. Amodiaquine-Artesunate versus Artemether-Lumefantrine against Uncomplicated Malaria in Children Less Than 14 Years in Ngaoundere, North Cameroon: Efficacy, Safety, and Baseline Drug Resistant Mutations in pfcrt, pfmdr1, and pfdhfr Genes Sun, 15 Dec 2013 15:44:00 +0000 Background. In Cameroon, both Artesunate-amodiaquine (AS/AQ) and artemether-lumefantrine (AL) are used as first-line treatment against uncomplicated malaria in line with the WHO recommendations. We compared the efficacy and safety of both therapeutic combinations and determined the prevalence of drug resistance conferring mutations in three parasite genes. Methods. One hundred and fifty acute malaria patients between six months and 14 years of age were randomized to receive standard doses of either AS/AQ (73) or AL (77) and followedup for 28 days. Outcome of treatment was according to the standard WHO classification. DNA samples from pretreatment parasite isolates were used to determine the prevalence of resistant mutations in the pfcrt, pfmdr1, and dhfr genes. Results. Both drug combinations induced rapid clearance of parasites and malaria symptoms. PCR-corrected cure rates were 100% and 96.4% for AL. The combinations were well tolerated. Major haplotypes included CVIET (71%), CVMNT (25%) for the pfcrt; SND (100%) for the pfmdr1; IRN (79, 8%), NCS (8.8%), and mixed haplotype (11, 8%) for the dhfr. Conclusion. Both AS/AQ and AL were highly effective and well tolerated for the treatment of uncomplicated falciparum malaria in Ngaoundere, Cameroon. High prevalence of mutant pfcrt alleles confirms earlier observations. Long-term monitoring of safety and efficacy and molecular markers is highly solicited. Innocent M. Ali, Palmer M. Netongo, Barbara Atogho-Tiedeu, Eric-Olivier Ngongang, Anthony Ajua, Eric A. Achidi, and Wilfred F. Mbacham Copyright © 2013 Innocent M. Ali et al. All rights reserved. Assessment of Clinical Diagnosis, Microscopy, Rapid Diagnostic Tests, and Polymerase Chain Reaction in the Diagnosis of Plasmodium falciparum in Nigeria Sun, 24 Nov 2013 10:10:56 +0000 This study compares the performance of clinical diagnosis and three laboratory diagnostic methods (thick film microscopy (TFM), rapid diagnostic test (RDT), and polymerase chain reaction (PCR)) for the diagnosis of Plasmodium falciparum in Nigeria. Using clinical criteria, 217 children were recruited into the study out of which 106 (48.8%) were positive by TFM, 84 (38.7%) by RDT, and 125 (57.6%) by PCR. Using a composite reference method generated from the three diagnostic methods, 71 (32.7%) patients were found to be truly infected and 90 (41.5%) truly uninfected, while 56 (25.8%) were misidentified as infected or noninfected. When each of the 3 diagnostic methods was compared with the composite reference, PCR had sensitivity of 97.3%, specificity of 62.5%, positive predictive value (PPV) of 56.8%, and negative predictive value (NPV) of 97.8%; microscopy had sensitivity of 77.2%, specificity of 72%, PPV of 66.9%, and NPV of 81.1%, while RDT had sensitivity of 62.3%, specificity of 87.4%, PPV of 67.7%, and NPV of 84.5%. PCR test performed best among the three methods followed by TFM and RDT in that order. The result of this study shows that clinical diagnosis cannot be relied upon for accurate diagnosis of P. falciparum in endemic areas. Olusola Ojurongbe, Olunike Olayeni Adegbosin, Sunday Samuel Taiwo, Oyebode Armstrong Terry Alli, Olugbenga Adekunle Olowe, Taiwo Adetola Ojurongbe, Oloyede Samuel Bolaji, and Oluwaseyi Adegboyega Adeyeba Copyright © 2013 Olusola Ojurongbe et al. All rights reserved. Why Hospital Pharmacists Have Failed to Manage Antimalarial Drugs Stock-Outs in Pakistan? A Qualitative Insight Mon, 07 Oct 2013 12:17:51 +0000 Purpose. This study aimed to explore the perceptions of hospital pharmacists towards drug management and reasons underlying stock-outs of antimalarial drugs in Pakistan. Methods. A qualitative study was designed to explore the perceptions of hospital pharmacists regarding drug management and irrational use of antimalarial drugs in two major cities of Pakistan, namely, Islamabad (national capital) and Rawalpindi (twin city). Semistructured interviews were conducted with 16 hospital pharmacists using indepth interview guides at a place and time convenient for the respondents. Interviews, which were audiotaped and transcribed verbatim, were evaluated by thematic content analysis and by other authors’ analysis. Results. Most of the respondents were of the view that financial constraints, inappropriate drug management, and inadequate funding were the factors contributing toward the problem of antimalarial drug stock-outs in healthcare facilities of Pakistan. The pharmacists anticipated that prescribing by nonproprietary names, training of health professionals, accepted role of hospital pharmacist in drug management, implementation of essential drug list and standard treatment guidelines for malaria in the healthcare system can minimize the problem of drug stock outs in healthcare system of Pakistan. Conclusion. The current study showed that all the respondents in the two cities agreed that hospital pharmacist has failed to play an effective role in efficient management of anti-malarial drugs stock-outs. Madeeha Malik, Mohamed Azmi Ahmad Hassali, Asrul Akmal Shafie, and Azhar Hussain Copyright © 2013 Madeeha Malik et al. All rights reserved. A Study on Course of Infection and Haematological Changes in falciparum-Infected in Comparison with Artemisinin(s)-Treated Mice Tue, 11 Jun 2013 09:04:54 +0000 To find out the efficacy and effect of artemisinin derivatives on haematological indices, C57BL/6J mice were challenged with Plasmodium falciparum and treated with therapeutic doses of AS, AE, and AL. Course of infection was studied in the infected and treated groups up to day 42. Peak level of parasitaemia (38%) was observed on day 11 in infected group. Haematological indices indicated significant () decrease in RBC, WBC, haemoglobin, packed cell volume, mean cell volume, and platelet counts in infected mice. But all the parameters were restored to normal values, and significant () changes were observed in all drug-treated groups. Insignificant changes were observed for MCHC () in all drug-treated groups. Percent of peak parasitaemia was much reduced in AL- (3.2% on day 3) treated group in comparison with AE- (2.4% on day 4) and AS- (4% on day 2) treated groups. Parasites were completely cleared on day 6 in AS group, day 5 in AE group, and day 4 in AL group. Hence, our results strongly support that combination therapy has high efficacy rates than monotherapy. No adverse effects were observed on haematological parameters when animals were treated with therapeutic dosages. Kalyan Kumar Kuthala, Sowjanya Meka, and Sunita Kanikaram Copyright © 2013 Kalyan Kumar Kuthala et al. All rights reserved. Malaria in Tunisian Military Personnel after Returning from External Operation Thu, 23 May 2013 17:53:15 +0000 Introduction. Malaria had been eliminated in Tunisia since 1979, but there are currently 40 to 50 imported cases annually. Soldiers are no exception as the incidence of imported malaria is increasing in Tunisian military personnel after returning from malaria-endemic area, often in Sub-Saharan Africa. Methods. We retrospectively analyzed the clinical and biological presentations, treatment, and outcomes of 37 Tunisian military personnel hospitalized at the Department of Internal Medicine, the Military Hospital of Tunis, between January 1993 and January 2011, for imported malaria. The clinical and laboratory features were obtained from the medical records and a questionnaire was filled by the patients about the compliance of malaria prophylaxis. Results. Thirty-seven male patients, with a mean age of 41 years, were treated for malaria infection. Twenty-two were due to Plasmodium falciparum. The outcome was favourable for all patients, despite two severe access. The long-term use of chemoprophylaxis has been adopted by only 21 (51%) of expatriate military for daily stresses. Moreover, poor adherence was found in 32 patients. Conclusion. The risk of acquiring malaria infection in Tunisian military personnel can largely be prevented by the regular use of chemoprophylactic drugs combined with protective measures against mosquito bites. Faïda Ajili, Riadh Battikh, Janet Laabidi, Rim Abid, Najeh Bousetta, Bouthaina Jemli, Nadia Ben abdelhafidh, Louzir Bassem, Saadia Gargouri, and Salah Othmani Copyright © 2013 Faïda Ajili et al. All rights reserved. Malariometric Survey of Ibeshe Community in Ikorodu, Lagos State: Dry Season Thu, 23 May 2013 16:19:34 +0000 Malariometric surveys generate data on malaria epidemiology and dynamics of transmission necessary for planning and monitoring of control activities. This study determined the prevalence of malaria and the knowledge, attitude, and practice (KAP) towards malaria infection in Ibeshe, a coastal community. The study took place during the dry season in 10 villages of Ibeshe. All the participants were screened for malaria. A semistructured questionnaire was used to capture sociodemographic data and KAP towards malaria. A total of 1489 participants with a mean age of years took part in the study. Malaria prevalence was 14.7% (95% CI 13.0–16.6%) with geometric mean density of 285 parasites/L. Over 97% of participants were asymptomatic. Only 40 (2.7%) of the participants were febrile, while 227 (18.1%) were anemic. Almost all the participants (95.8%) identified mosquito bite as a cause of malaria, although multiple agents were associated with the cause of malaria. The commonest symptoms associated with malaria were hot body (89.9%) and headache (84.9%). Window nets (77.0%) were preferred to LLIN (29.6%). Malaria is mesoendemic in Ibeshe during the dry season. The participants had good knowledge of symptoms of malaria; however, there were a lot of misconceptions on the cause of malaria. Oluwagbemiga O. Aina, Chimere O. Agomo, Yetunde A. Olukosi, Hilary I. Okoh, Bamidele A. Iwalokun, Kathleen N. Egbuna, Akwaowo B. Orok, Olusola Ajibaye, Veronica N. V. Enya, Samuel K. Akindele, Margaret O. Akinyele, and Philip U. Agomo Copyright © 2013 Oluwagbemiga O. Aina et al. All rights reserved. Expanding Access to Malaria Diagnosis through Retail Shops in Western Kenya: What Do Shop Workers Think? Tue, 21 May 2013 13:14:56 +0000 Background. The common symptoms of malaria reduce the specificity of clinical diagnosis. Presumptive treatment is conventional but can lead to overdiagnosis of malaria, delay of appropriate treatment, overprescription of antimalarials, and drug resistance. Routine use of diagnostic tests can address many of these concerns. Though treatment is often procured from retailers, there is low availability of rapid diagnostic tests for malaria (MRDTs), a simple, inexpensive, and accurate diagnostic solution. We know little about the challenges to expanding access to diagnostics through these outlets. Methods. To understand the perceptions of the benefits and challenges to selling rapid diagnostic tests for malaria, we conducted focus group discussions with antimalarial retailers who serve the residents of the Webuye Health and Demographic Surveillance Site in western Kenya. Results. Medicine retailers perceived MRDTs to be beneficial to their customers and businesses but also included cost, fear of the tests, risks of self-treatment, and regulatory concerns among the challenges to using and selling MRDTs. Conclusion. MRDTs represent a viable approach to increase access to malaria diagnostic testing. Medicine retailers are eager for MRDTs to be made available to them. However, certain challenges remain to implementation in retail outlets and should be addressed in advance. Andria Rusk, Catherine Goodman, Violet Naanyu, Beatrice Koech, Andrew Obala, and Wendy Prudhomme O'Meara Copyright © 2013 Andria Rusk et al. All rights reserved. Formulation and Particle Size Reduction Improve Bioavailability of Poorly Water-Soluble Compounds with Antimalarial Activity Sun, 12 May 2013 17:49:25 +0000 Decoquinate (DQ) is highly effective at killing malaria parasites in vitro; however, it is extremely insoluble in water. In this study, solid dispersion method was used for DQ formulation which created a suitable physical form of DQ in aqueous phase for particle manipulation. Among many polymers and surfactants tested, polyvinylpyrrolidone 10, a polymer, and L-α-phosphatidylcholine or polysorbate, two surfactants, were chosen as DQ formulation components. The formulation particles were reduced to a mean size between 200 to 400 nm, which was stable in aqueous medium for at least three weeks. Pharmacokinetic (PK) studies showed that compared to DQ microparticle suspension, a nanoparticle formulation orally dosed to mice showed a 14.47-fold increase in area under the curve (AUC) of DQ plasma concentration and a 4.53-fold increase in AUC of DQ liver distribution. WR 299666, a poorly water-soluble compound with antimalarial activity, was also tested and successfully made into nanoparticle formulation without undergoing solid dispersion procedure. We concluded that nanoparticles generated by using appropriate formulation components and sufficient particle size reduction significantly increased the bioavailability of DQ and could potentially turn this antimalarial agent to a therapeutic drug. Hongxing Wang, Qigui Li, Sean Reyes, Jing Zhang, Lisa Xie, Victor Melendez, Mark Hickman, and Michael P. Kozar Copyright © 2013 Hongxing Wang et al. All rights reserved. Protective Effect of Quercetin on Chloroquine-Induced Oxidative Stress and Hepatotoxicity in Mice Wed, 27 Mar 2013 10:38:51 +0000 The present study was aimed to find out the protective effect of quercetin on hepatotoxicity resulting by commonly used antimalarial drug chloroquine (CQ). Swiss albino mice were administered with different amounts of CQ ranging from human therapeutic equivalent of 360 mg/kg body wt. to as high as 2000 mg/kg body wt. We observed statistically significant generation of reactive oxygen species, liver toxicity, and oxidative stress. Our observation of alterations in biochemical parameters was strongly supported by real-time PCR measurement of mRNA expression of key biochemical enzymes involved in hepatic toxicity and oxidative stress. However, the observed hepatotoxicity and accompanying oxidative stress following CQ administration show dose specific pattern with little or apparently no effect at therapeutic dose while having severe effects at higher dosages. We further tested quercetin, an antioxidant flavanoid, against CQ-induced hepatoxicity and found encouraging results as quercetin was able to drastically reduce the oxidative stress and hepatotoxicity resulting at higher dosages of CQ administration. In conclusion, our study strongly suggests co administration of antioxidant flavonoid like quercetin along with CQ for antimalarial therapy. This is particularly important when CQ is administered as long-term prophylactic treatment for malaria as chronic exposure has shown to be resulting in higher dose level of drug in the body. Shrawan Kumar Mishra, Prabhat Singh, and Srikanta Kumar Rath Copyright © 2013 Shrawan Kumar Mishra et al. All rights reserved. Selective Intermittent Preventive Treatment of Vivax Malaria: Reduction of Malaria Incidence in an Open Cohort Study in Brazilian Amazon Thu, 21 Mar 2013 14:22:18 +0000 In children, the Intermittent Preventive Treatment (IPTc), currently called Seasonal Malaria Chemoprevention (SMC), was considered effective on malaria control due to the reduction of its incidence in Papua New Guinea and in some areas with seasonal malaria in Africa. However, the IPT has not been indicated because of its association with drug resistance and for hindering natural immunity development. Thus, we evaluated the alternative IPT impact on malaria incidence in three riverside communities on Madeira River, in the municipality of Porto Velho, RO. We denominate this scheme Selective Intermittent Preventive Treatment (SIPT). The SIPT consists in a weekly dose of two 150 mg chloroquine tablets for 12 weeks, for adults, and an equivalent dose for children, after complete supervised treatment for P. vivax infection. This scheme is recommend by Brazilian Health Ministry to avoid frequent relapses. The clinic parasitological and epidemiological surveillance showed a significant reduction on vivax malaria incidence. The results showed a reduction on relapses and recurrence of malaria after SIPT implementation. The SIPT can be effective on vivax malaria control in localities with high transmission risk in the Brazilian Amazon. Tony Hiroshi Katsuragawa, Luiz Herman Soares Gil, Alzemar Alves de Lima, Elci Marlei Freitag, Tatiana Marcondes dos Santos, Maria Teixeira do Nascimento Filha, Alcides Procópio Justiniano dos Santos Júnior, Josiane Mendes da Silva, Aline de Freitas Rodrigues, Mauro Shugiro Tada, Cor Jesus Fernandes Fontes, and Luiz Hildebrando Pereira da Silva Copyright © 2013 Tony Hiroshi Katsuragawa et al. All rights reserved. Malariometric Indices among Nigerian Children in a Rural Setting Thu, 28 Feb 2013 18:15:12 +0000 Malaria contributes to high childhood morbidity and mortality in Nigeria. To determine its endemicity in a rural farming community in the south-south of Nigeria, the following malariometric indices, namely, malaria parasitaemia, spleen rates, and anaemia were evaluated in children aged 2–10 years. This was a descriptive cross-sectional survey among school-age children residing in a rubber plantation settlement. The children were selected from six primary schools using a multistaged stratified cluster sampling technique. They were all examined for pallor, enlarged spleen, or liver among other clinical parameters and had blood films for malaria parasites. Of the 461 children recruited, 329 (71.4%) had malaria parasites. The prevalence of malaria parasitaemia was slightly higher in the under fives than that of those ≥5 years, 76.2% and 70.3%, respectively. Splenic enlargement was present in 133 children (28.9%). The overall prevalence of anaemia was 35.7%. Anaemia was more common in the under-fives (48.8%) than in those ≥5 years (32.8%). The odds of anaemia in the under fives were significantly higher than the odds of those ≥5 years ( [1.19–3.18]). Malaria is highly endemic in this farming community and calls for intensification of control interventions in the area with special attention to school-age children. Ekong E. Udoh, Angela E. Oyo-ita, Friday A. Odey, Komomo I. Eyong, Chioma M. Oringanje, Olabisi A. Oduwole, Joseph U. Okebe, Ekpereonne B. Esu, Martin M. Meremikwu, and Asindi A. Asindi Copyright © 2013 Ekong E. Udoh et al. All rights reserved. Management of Uncomplicated Malaria in Underfives in Private and Public Health Facilities in South-Eastern Nigeria: A Clinical Audit of Current Practices Mon, 21 Jan 2013 13:54:16 +0000 Malaria remains a leading cause of underfive morbidity and mortality in sub-Saharan Africa. Effective case management is a strategy recommended by the World Health Organization for its control. A clinical audit of case management of uncomplicated malaria in underfives in health facilities in Cross River State, Nigeria, was conducted from January to March 2012. Data was extracted from patients’ case records by trained medical personnel using pretested data extraction forms. Of the 463 case records reviewed, age, gender, and weight were reported in 98.1%, 97.3%, and 49.7% of the children, respectively. A history of fever was obtained in 89.6% and a record of temperature in 74.1% of the children. General examination was performed in 203 (43.8%) children. Malaria parasite test was requested in 132 (28.5%) while Packed cell volume or haemoglobin was requested in 107 (23.1%) children. Appropriate dose of Artemisinin Combination Therapy (ACT) was instituted in 300 (64.8%), wrong dose in 109 (23.5%), and inappropriate treatment in 41 (8.9%). The utilization of ACTs for treating uncomplicated malaria in the State has improved but clinical assessment of patients and laboratory confirmation of diagnosis are suboptimum. Ekong Udoh, Angela Oyo-ita, Friday Odey, Emmanuel Effa, Ekpereonne Esu, Olabisi Oduwole, Moriam Chibuzor, and Martin Meremikwu Copyright © 2013 Ekong Udoh et al. All rights reserved. Clinical Efficacy of Artemether-Lumefantrine in Congolese Children with Acute Uncomplicated Falciparum Malaria in Brazzaville Mon, 17 Dec 2012 14:45:24 +0000 The Republic of the Congo adopted artemisinin-based combination therapies (ACTs) in 2006: artesunate-amodiaquine and artemether-lumefantrine as the first-line and second-line drugs, respectively. The baseline efficacy of artemether-lumefantrine was evaluated between March and July 2006 in Brazzaville, the capital city of Congo. Seventy-seven children aged between 6 months and 10 years were enrolled in a nonrandomized study. The children were treated under supervision with 6 doses of artemether-lumefantrine and followed up for 28 days in accordance with the 2003 World Health Organization guideline. Pretreatment (i.e., day 0) and recrudescent Plasmodium falciparum isolates between day 14 and day 28 were compared by the polymerase chain reaction to distinguish between true recrudescence and reinfection. The overall cure rate on day 28 was 96.9% after PCR correction. Reported adverse effects included pruritus and dizziness. Artemether-lumefantrine was highly efficacious in Brazzaville. Mathieu Ndounga, Rachida Tahar, Prisca N. Casimiro, Dieudonné Loumouamou, and Leonardo K. Basco Copyright © 2012 Mathieu Ndounga et al. All rights reserved. Efficacy of Eosin B as a New Antimalarial Drug in a Murine Model Sun, 16 Dec 2012 14:55:57 +0000 The initial success of any adopted anti-infective strategy to malaria is followed by a descent due to the emergence of resistance to it. The search for new drugs and drug targets is a consistent demand in this disease. Eosin B, a common laboratory dye, is reported to have good antiparasitic properties in vitro. It was studied for its antiparasitic effect in vivo on chloroquine-sensitive Plasmodium berghei murine malaria. Eosin B was administered in 2 different doses by either the oral or parenteral route, once or twice daily to mice infected with Plasmodium berghei. Both the doses of eosin B 400 mg/kg and 800 mg/kg gave better results than the controls which were 40 mg/kg chloroquine and 100 mg/kg of arteether with significance. Percentage suppressive activity by Peter’s test of eosin B was better, though at a higher dose than both the controls. Survival rate of mice receiving the higher dose of eosin B was longer than that of the controls. When administered twice daily, the mice were fully cured after 4 days. Eosin B seems to be a promising drug exhibiting good antimalarial effects in the murine model of the disease. Zahra Zamani, Alireza Sadeghi Tafreshi, Hossein Nahrevanian, Behzad Lame-Rad, Fatemeh Pourfallah, Hossein Eslamifar, Sedigheh Sadeghi, Farideh Vahabi, Ayda Iravani, and Mohammad Arjmand Copyright © 2012 Zahra Zamani et al. All rights reserved. Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF-B Translocation in a Mechanism Independent of Plasmodium Killing Thu, 11 Oct 2012 16:06:06 +0000 Artemisinin and its derivates are an important class of antimalarial drug and are described to possess immunomodulatory activities. Few studies have addressed the effect of artesunate in the murine malaria model or its effect on host immune response during malaria infection. Herein, we study the effect of artesunate treatment and describe an auxiliary mechanism of artesunate in modulating the inflammatory response during experimental malaria infection in mice. Treatment with artesunate did not reduce significantly the parasitemia within 12 h, however, reduced BBB breakdown and TNF-α mRNA expression in the brain tissue of artesunate-treated mice. Conversely, mefloquine treatment was not able to alter clinical features. Notably, artesunate pretreatment failed to modulate the expression of LFA-1 in splenocytes stimulated with parasitized red blood cells (pRBCs) in vitro; however, it abrogated the expression of ICAM-1 in pRBC-stimulated endothelial cells. Accordingly, a cytoadherence in vitro assay demonstrated that pRBCs did not adhere to artesunate-treated vascular endothelial cells. In addition, NF-κB nuclear translocation in endothelial cells stimulated with pRBCs was impaired by artesunate treatment. Our results suggest that artesunate is able to exert a protective effect against the P. berghei-induced inflammatory response by inhibiting NF-κB nuclear translocation and the subsequent expression of ICAM-1. Mariana C. Souza, Flávio Henrique Marcolino Paixão, Fausto K. Ferraris, Isabela Ribeiro, and Maria das Graças M. O. Henriques Copyright © 2012 Mariana C. Souza et al. All rights reserved.