Malaria Research and Treatment

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.

Protective Effect of Quercetin on Chloroquine-Induced Oxidative Stress and Hepatotoxicity in Mice

Shrawan Kumar Mishra, Prabhat Singh, and Srikanta Kumar Rath — 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.

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.

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.

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.

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.

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.

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.

In Vitro Chloroquine Resistance in Plasmodium falciparum Isolates from Tertiary Care Hospital

Mon, 24 Sep 2012 14:31:14 +0000

Chloroquine (CQ) has been the mainstay of treatment of malaria for decades. This cost-effective and safe drug has become ineffective for treatment of falciparum malaria in many parts of the world due to development of resistance by the parasite. In addition CQ is not gametocytocidal for P. falciparum and thus cannot block transmission. The extent of problem of chloroquine resistance in P. falciparum is increasing every year. The study was done in period of 2 years. A total of 5653 specimens were examined for malarial infection by employing different diagnostic modalities. Four hundred and thirty-five were found to be positive for P. falciparum by using different diagnostic techniques. All positive specimens were cultured on RPMI 1640 medium; only 108 were found to be culture positive. Sensitivity of isolates to chloroquine was done using Mark III WHO sensitivity plates. The prevalence of malaria infection was found 9.54% in 2010. There were schizont formation at 8 pmol/liter or more of chloroquine concentration in 26 isolates. The emergence of chloroquine (CQ) resistance pattern in Aligarh isolates increases. Antimalarial agents should be used with caution; monotherapies should be avoided.

Subacute Therapeutic Dosing of Artemether-Lumefantrine and Artesunate-Amodiaquine Combination Preserves Plasma Cholesterol, Renal Antioxidant Status, and Organ Weights in Rats

Chiagoziem A. Otuechere, Gloria Edewor, Oluwafemi Ezekiel Kale, and Martins Ekor — Tue, 10 Jul 2012 11:29:25 +0000

Recent instances of breakdowns of malaria control programs and the constant emergence of drug-resistant parasites to monotherapies have shored up the use of artemisinin-based combination therapy (ACT) as the malaria therapy of choice. We evaluated a subacute therapeutic dosing of artemether-lumefantrine and artesunate-amodiaquine on plasma cholesterol, renal antioxidants, and organ weights in rats. Sixteen albino rats were grouped into three. Group A (𝑛=5) served as the control. Groups B (𝑛=6) and C (𝑛=5) were administered, twice daily, oral therapeutic doses of artemether-lumefantrine (1.14/6.86 mg/kg/d) and artesunate-amodiaquine (2.86/8.58 mg/kg/d), respectively, for seven days. From our results, ACTs did not significantly (𝑃>0.05) alter catalase, superoxide dismutase, glutathione S-transferase, myeloperoxidase, and total glutathione levels when compared with the control. Plasma total cholesterol levels also decreased insignificantly (𝑃>0.05). Organ-system weights were not significantly (𝑃>0.05) different from control rats. Artesunate-amodiaquine, but not artemether-lumefantrine, significantly increased (𝑃<0.05) lactate dehydrogenase activity and also afforded a 27.2% decrease in heart weight when compared with control. Also, both ACTs increased (𝑃<0.05) lipid peroxidation. Overall, artesunate-amodiaquine and artemether-lumefantrine may preserve renal antioxidants and organ weights in vivo. However, caution is required above therapeutic indications or in chronic doses as this may predispose to renal oxidative stress.

Thrombocytopenia as an Indicator of Malaria in Adult Population

Shiraz Jamal Khan, Yasir Abbass, and Mumtaz Ali Marwat — Mon, 02 Jul 2012 08:08:31 +0000

Objectives. To evaluate the predictive value of thrombocytopenia in malaria. Patients and Methods. It was a prospective observational study on all febrile patients with thrombocytopenia presenting to the Medical Unit of Hayat Abad Medical Complex during November 2008 to November 2010. Results. Of the total of 228 patients with fever and thrombocytopenia, 121 patients (53%) proved to be suffering from malaria. Of them 82 patients (68%) had falciparum malaria while 39 patients (32%) had vivax infection. Of these 121 patients, platelet counts ranged between 25,000 and 150,000/dL with a mean value of 101,000/dL (SD±47,500) and a median of 75,000/dL. Of the 107 patients who were not suffering from malaria, the counts ranged between 10,000 and 150,000/dL with a mean value of 58,000/dL (SD±54,000) and median of 50,000/dL. Conclusions. The presence of thrombocytopenia may be a predictor of malaria in adult population.

Comparative Study on the Effects of Chloroquine and Artesunate on Histopathological Damages Caused by Plasmodium berghei in Four Vital Organs of Infected Albino Mice

O. T. Soniran, O. A. Idowu, O. L. Ajayi, and I. C. Olubi — Sun, 24 Jun 2012 09:50:50 +0000

The aim of the present study was to investigate the positive influence of chloroquine and artesunate on the pathological damages caused by Plasmodium berghei on vital organs of mice in an established infection. Healthy adult albino mice with average weight of 25 g were used for the study. Treated group was administered orally with 100 mg/kg of chloroquine and artesunate, respectively. Control animals were given water for the same period. Histological examination of the liver, spleen, lungs, and kidney revealed absence of accumulation of iron (haemosiderosis) in the liver, thickened alveolar wall, and interstitial mononuclear cells infiltration in the lungs of the artesunate group, while absence of emphysema in the lungs and megakaryoblast hyperplasia in the spleen was observed in the chloroquine group. Lymphoid hypoplasia in the chloroquine group and megakayoblast hyperplasia in the artesunate group were observed but not in the control group. Thus, the use of these drugs especially under the practice of self-medication should be prohibited in lands where they are still in use as antimalaria medicine.

Failure of Supervised Chloroquine and Primaquine Regimen for the Treatment of Plasmodium vivax in the Peruvian Amazon

Thu, 31 May 2012 15:24:11 +0000

The widespread use of primaquine (PQ) and chloroquine (CQ), together, may be responsible for the relatively few, isolated cases of chloroquine-resistant P. vivax (CQRPV) that have been reported from South America. We report here a case of P. vivax from the Amazon Basin of Peru that recurred against normally therapeutic blood levels of CQ. Four out of 540 patients treated with combination CQ and PQ had a symptomatic recurrence of P. vivax parasitemia within 35 days of treatment initiation, possibly indicating CQ failure. Whole blood total CQ level for one of these four subjects was 95 ng/ml on the day of recurrence. Based on published criteria that delineate CQRPV as a P. vivax parasitemia, either recrudescence or relapse, that appears against CQ blood levels >100 ng/mL, we document the occurrence of a P. vivax strain in Peru that had unusually high tolerance to the synergistic combination therapy of CQ + PQ that normally works quite well.

Therapeutic Efficacy of Artemether-Lumefantrine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Northern Ethiopia

Gebremedhin Kinfu, Solomon Gebre-Selassie, and Nigus Fikrie — Wed, 11 Apr 2012 18:33:08 +0000

Introduction. Multidrug resistance of Plasmodium falciparum is spreading throughout Africa. This has posed major challenges to malaria control in sub-Saharan Africa. Objective. The aim of the study was to evaluate the efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in North Ethiopia. Methods. This prospective study was undertaken during August–November 2009 on 71 malaria patients that fulfilled the inclusion criteria set by the WHO. Patients were followed up for 28 days. Thick and thin blood films were prepared by Giemsa stain for microscopy to determine parasite density. A standard six-dose regimen of artemether-lumefantrine was administered over three days and was followed up with clinical and parasitological evaluations over 28 days. Results. The cure rate (ACPR) was found to be high (97.2%) in this study. The parasite and fever clearance time was also rapid. Artemether-lumefantrine for the treatment of acute uncomplicated Plasmodium falciparum malaria in the study area showed 97.2% cure rate and only 2.8% failure rate. Conclusion. The result showed that the drug could continue as first line for the treatment of uncomplicated Plasmodium falciparum malaria in the study area. The efficacy of artemether-lumefantrine needs to be carefully monitored periodically in sentinel sites representing different areas of the country.

In Vivo Hemozoin Kinetics after Clearance of Plasmodium berghei Infection in Mice

Rosangela Frita, Daniel Carapau, Maria M. Mota, and Thomas Hänscheid — Wed, 11 Apr 2012 11:32:24 +0000

Hemozoin (Hz) is released into the blood stream after rupture of infected red blood cells (iRBCs) at the end of each parasite replication cycle. This free Hz is ingested by circulating and resident phagocytes. The presence of Hz in tissues after clearance of infection has been previously reported. Still, little is known about the kinetics of Hz in vivo, during and after Plasmodium infection. It is particularly important to understand Hz kinetics after malaria infections as it has been reported that Hz is associated with impairment of immune functions, including possible consequences for coinfections. Indeed, if Hz remains biologically active for prolonged periods of time inside immunocompetent cells, the potential consequences of such accumulation and presence to the immune system should be clarified. Here, using several independent methods to assess the presence of Hz, we report the long-term in vivo kinetics of Hz in diverse organs in a murine model of malaria infection.

Malaria Knowledge, Concern, Land Management, and Protection Practices among Land Owners and/or Managers in Lowland versus Highland Ecuador

Lauren L. Pinault and Fiona F. Hunter — Thu, 26 Jan 2012 09:24:28 +0000

To control malaria effectively, it is essential to understand the current knowledge, beliefs, concerns, land management practices, and mosquito bite protection methods in use by citizens. This study presents a comparative, quantitative, interview-based study of land owners and/or managers (𝑛=262) in the Ecuadorian lowlands (presently considered malarious) (𝑛=131) and highlands (potentially malarious in the future) (𝑛=131). Although respondents had a strong understanding of where the disease occurs in their own country and of the basic relationship among standing water, mosquitoes, and malaria, about half of respondents in potential risk areas denied the current possibility of malaria infection on their own property. As well, about half of respondents with potential anopheline larval habitat did not report its presence, likely due to a highly specific definition of suitable mosquito habitat. Most respondents who are considered at risk of malaria currently use at least one type of mosquito bite prevention, most commonly bed nets.

Health Care Seeking Behavior among Caregivers of Sick Children Who Had Cerebral Malaria in Northwestern Nigeria

Thu, 26 Jan 2012 08:06:06 +0000

Cerebral malaria is a significant cause of childhood morbidity in our region. The challenges of effective management include time and quality of treatment. The study appraised the health care seeking behavior of caregivers of sick children who developed cerebral malaria, in Zaria, northwestern Nigeria. Caregivers indentified were parents 29 (87.9%) and grandparents 4 (12.1%). Most of them were in the upper social classes. Health care options utilized before presentation at our facility were formal health facility 24 (72.7%), patent medicine seller 12 (36.4%), home treatment 10 (30.3%), and herbal concoction 6 (18.2%) with majority 24 (72.7%) using more than one option. Antimalarial therapy was instituted in 25 (75.6%) of the cases. Mortality was significantly associated with the use of herbal concoction, treatment at a formal health facility and patent medicine seller, multiple convulsions, age less than 5 years, and noninstitution of antimalarial therapy before presentation. The study showed use of inappropriate health care options by caregivers and highlighted the need to pursue an awareness drive among caregivers on the use of health care options.

Antimalarial Effects of Iranian Flora Artemisia sieberi on Plasmodium berghei In Vivo in Mice and Phytochemistry Analysis of Its Herbal Extracts

Mon, 23 Jan 2012 11:25:15 +0000

The aim of this study is pharmacochemistry of Iranian flora Artemisia sieberi and its antimalarial effects on Plasmodium berghei in vivo. This is the first application of A. sieberi for treatment of murine malaria. A. sieberi were collected at flowering stage from the Khorassan and Semnan provinces of Iran; the aerial parts were air-dried at room temperature and then powdered. The powder was macerated in methanol, filtered with Bokhner hopper and solvent was separated in rotary evaporator. Total herbal extract was subsequently processed for ether and chloroform extracts preparation. The toxicity of herbal extract was assessed on naive NMRI mice with high, average and low doses; then pathophysiological signs were assessed. Finally, the antimalarial efficacy was investigated on two groups of Plasmodium berghei infected mice. Percentage of parasitaemia and pathophysiology were also evaluated. The results of this assessment showed no toxicity even by high concentration of herbal extract. A significant reduction in percentage of parasitaemia was observed; no alterations of hepatosplenomegaly and body weight were indicated in study group. A. sieberi extracts showed antimalarial effects against murine malaria with some efficacies on reducing pathophysiology. However, there is requirement to find the major component of this herbal extract by further studies.

Medicinal Plants Used by Various Tribes of Bangladesh for Treatment of Malaria

Mon, 23 Jan 2012 11:23:33 +0000

It has been estimated that 300–500 million malaria infections occur on an annual basis and causes fatality to millions of human beings. Most of the drugs used for treatment of malaria have developed drug-resistant parasites or have serious side effects. Plant kingdom has throughout the centuries proved to be efficient source of efficacious malarial drugs like quinine and artemisinin. Since these drugs have already developed or in the process of developing drug resistance, it is important to continuously search the plant kingdom for more effective antimalarial drugs. In this aspect, the medicinal practices of indigenous communities can play a major role in identification of antimalarial plants. Bangladesh has a number of indigenous communities or tribes, who because of their living within or in close proximity to mosquito-infested forest regions, have high incidences of malaria. Over the centuries, the tribal medicinal practitioners have treated malaria with various plant-based formulations. The objective of the present study was to conduct an ethnomedicinal survey among various tribes of Bangladesh to identify the plants that they use for treatment of the disease. Surveys were conducted among seven tribes, namely, Bawm, Chak, Chakma, Garo, Marma, Murong, and Tripura, who inhabit the southeastern or northcentral forested regions of Bangladesh. Interviews conducted with the various tribal medicinal practitioners indicated that a total of eleven plants distributed into 10 families were used for treatment of malaria and accompanying symptoms like fever, anemia, ache, vomiting, and chills. Leaves constituted 35.7% of total uses followed by roots at 21.4%. Other plant parts used for treatment included barks, seeds, fruits, and flowers. A review of the published scientific literature showed that a number of plants used by the tribal medicinal practitioners have been scientifically validated in their uses. Taken together, the plants merit further scientific research towards possible discovery of novel compounds that can be used to successfully treat malaria with less undesirable sideeffects.

Prospects and Pitfalls of Pregnancy-Associated Malaria Vaccination Based on the Natural Immune Response to Plasmodium falciparum VAR2CSA-Expressing Parasites

Elizabeth G. Kane and Andrew W. Taylor-Robinson — Wed, 18 Jan 2012 14:54:21 +0000

Pregnancy-associated malaria, a manifestation of severe malaria, is the cause of up to 200,000 infant deaths a year, through the effects of placental insufficiency leading to growth restriction and preterm delivery. Development of a vaccine is one strategy for control. Plasmodium falciparum-infected red blood cells accumulate in the placenta through specific binding of pregnancy-associated parasite variants that express the VAR2CSA antigen to chondroitin sulphate A on the surface of syncytiotrophoblast cells. Parasite accumulation, accompanied by an inflammatory infiltrate, disrupts the cytokine balance of pregnancy with the potential to cause placental damage and compromise foetal growth. Multigravid women develop immunity towards VAR2CSA-expressing parasites in a gravidity-dependent manner which prevents unfavourable pregnancy outcomes. Although current vaccine design, targeting VAR2CSA antigens, has succeeded in inducing antibodies artificially, this candidate may not provide protection during the first trimester and may only protect those women living in areas endemic for malaria. It is concluded that while insufficient information about placental-parasite interactions is presently available to produce an effective vaccine, incremental progress is being made towards achieving this goal.

Plasmodium falciparum: Assessment of Selectivity of Action of Chloroquine, Alchornea cordifolia, Ficus polita, and Other Drugs by a Tetrazolium-Based Colorimetric Assay

Nana Kofi Ayisi, Regina Appiah-Opong, Ben Gyan, Kwasi Bugyei, and Fred Ekuban — Thu, 01 Dec 2011 15:21:37 +0000

A tetrazolium-based colorimetric selective assay (MTT-based CSA) was developed to assess the selectivity of antimalarial drugs. This in vitro assay, unlike all others, measures the ability of drugs to indirectly protect red blood cells (RBCs) from Plasmodium-falciparum-induced destruction. Optimum incubation time and number of cells needed were 5 days and 23×106 RBCs per well, respectively. A parasitemia range of 0.375% to 3% was found to be suitable for this assay. The MTT-based CSA determined anti-P. falciparum strain DD2 activity of chloroquine at a higher 50% effective concentration (EC50) value (21.0 𝜇g/mL) than the isotopic microtest (10.0 𝜇g/mL). Artesunate and oxytetracycline achieved 90% effect against DD2 with minimal or no toxicity to RBCs. Against chloroquine sensitive strain 3D7, chloroquine and Alchornea cordifolia had EC50 values of 0.025 𝜇g/mL and 4.9 𝜇g/mL respectively, and selective index (SI) values of >2,000 and >69.4 𝜇g/mL, respectively.

Parasitologic Assessment of Two-Dose and Monthly Intermittent Preventive Treatment of Malaria during Pregnancy with Sulphadoxine-Pyrimethamine (IPTP-SP) in Lagos, Nigeria

Chimere O. Agomo, Wellington A. Oyibo, and Funke Odukoya-Maije — Wed, 26 Oct 2011 13:46:00 +0000

Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine (IPTP-SP) is a key strategy in the control of malaria in pregnancy. However, reports of increasing level of resistance to SP using nonpregnant populations have made it imperative for the continuous monitoring of the efficacy of SP in pregnant women. This study assessed using microscopy, monthly dosing and the standard two-dose regimen among 259 pregnant women attending antenatal clinics in Lagos, Nigeria that consented 122 in the two-dose arm (Arm A) and 137 in the monthly dose arm (Arm B). Baseline parasitaemia in the two groups was 5 (4.1%) and 3 (2.2%) in Arms A and B, respectively. Few of the women developed parasitaemia after the initial SP dose in Arms A 4 (3.3%) and B 2 (1.5%). However, none of the women had malaria infection after the second dose in both Arms. Although IPTP-SP is suggestive of protecting the women from malaria infection, there was no significant difference observed between the two dosing schemes.

Characterization of the Duffy-Binding-Like Domain of Plasmodium falciparum Blood-Stage Antigen 332

Mon, 19 Sep 2011 13:14:08 +0000

Studies on Pf332, a major Plasmodium falciparum blood-stage antigen, have largely been hampered by the cross-reactive nature of antibodies generated against the molecule due to its high content of repeats, which are present in other malaria antigens. We previously reported the identification of a conserved domain in Pf332 with a high degree of similarity to the Duffy-binding-like (DBL) domains of the erythrocyte-binding-like (EBL) family. We here describe that antibodies towards Pf332-DBL are induced after repeated exposure to P. falciparum and that they are acquired early in life in areas of intense malaria transmission. Furthermore, a homology model of Pf332-DBL was found to be similar to the structure of the EBL-DBLs. Despite their similarities, antibodies towards Pf332-DBL did not display any cross-reactivity with EBL-proteins as demonstrated by immunofluorescence microscopy, Western blotting, and peptide microarray. Thus the DBL domain is an attractive region to use in further studies on the giant Pf332 molecule.

Malaria Treatment Policy Change and Implementation: The Case of Uganda

Mon, 19 Sep 2011 11:47:36 +0000

Malaria due to P. falciparum is the number one cause of morbidity and mortality in Uganda where it is highly endemic in 95% of the country. The use of efficacious and effective antimalarial medicines is one of the key strategies for malaria control. Until 2000, Chloroquine (CQ) was the first-line drug for treatment of uncomplicated malaria in Uganda. Due to progressive resistance to CQ and to a combination of CQ with Sulfadoxine-Pyrimethamine, Uganda in 2004 adopted the use of ACTs as first-line drug for treating uncomplicated malaria. A review of the drug policy change process and postimplementation reports highlight the importance of managing the policy change process, generating evidence for policy decisions and availability of adequate and predictable funding for effective policy roll-out. These and other lessons learnt can be used to guide countries that are considering anti-malarial drug change in future.

Knowledge and Misconceptions about Malaria among Pregnant Women in a Post-Conflict Internally Displaced Persons' Camps in Gulu District, Northern Uganda

James Obol, Kitara David Lagoro, and Orach Christopher Garimoi — Wed, 14 Sep 2011 10:29:43 +0000

Background. In Uganda Malaria continues to be a major public health problem accounting for about 30–50% of all outpatient consultations and 35% of hospital admissions and a leading cause of mortality and morbidity. Pregnant women and their unborn children are vulnerable to malaria. Methods. A cross-sectional survey was conducted in 20 postconflict IDP camps of Gulu district selected randomly as clusters. 769 pregnant women were interviewed. Results. The majority of the respondents 85% have ever heard about malaria. Most (80%) 571 respondent attributed malaria to be transmitted by mosquito bites, 15 said cold weather, 53 said dirt, and 35 said not sleeping under net. Most (91%) 683 respondents mentioned that malaria was caused by mosquito, 28 mentioned cold food, 3 mentioned playing in the rain, 19 mentioned cold weather, and 6 mentioned eating mangos. Conclusion. Most pregnant women in the post conflict IDP camps have relatively high knowledge about malaria transmission, signs, symptoms, and consequences during pregnancy. However, majority of respondents had misconception about the cause of malaria while a few had misconception about the mode of malaria transmission.

Pattern of the Antimalarials Prescription during Pregnancy in Bangui, Central African Republic

Fri, 15 Jul 2011 12:19:19 +0000

Introduction. The aim of this study was to identify the antimalarials prescribed during the pregnancy and to document their timing. Method. From June to September 2009, a survey was conducted on 565 women who gave birth in the Castors maternity in Bangui. The antenatal clinics cards were checked in order to record the types of antimalarials prescribed during pregnancy according to gestational age. Results. A proportion of 28.8% ANC cards contained at least one antimalarial prescription. The commonest categories of antimalarials prescribed were: quinine (56.7%), artemisinin-based combinations (26.8%) and artemisinin monotherapy (14.4%). Among the prescriptions that occurred in the first trimester of pregnancy, artemisinin-based combinations and artemisinin monotherapies represented the proportions of (10.9%) and (13.3%). respectively. Conclusion. This study showed a relatively high rate (>80%) of the recommended antimalarials prescription regarding categories of indicated antimalarials from national guidelines. But, there is a concern about the prescription of the artemisinin derivatives in the first trimester of pregnancy, and the prescription of artemisinin monotherapy. Thus, the reinforcement of awareness activities of health care providers on the national malaria treatment during pregnancy is suggested.

Factors Associated with Use of Guideline in Home Management of Malaria among Children in Rural South West Nigeria

Thu, 14 Jul 2011 17:51:29 +0000

The dosage regimen for artemether-lumefantrine which is the standard of care for malaria in most of Sub-Saharan countries requires use of treatment guidelines and instructions to enhance caregivers' performance in the treatment of malaria. As part of a larger study evaluating its effectiveness in a rural local government area in southwestern Nigeria, 552 caregivers whose children had fever two weeks preceeding the survey were recruited. Information was collected with interviewer administered questionnaire. A multilevel logistic regression model was fitted using the gllamm approach in Stata to determine the factors associated with use of guideline. Age and educational background of caregiver were significantly associated with guideline use. Caregivers aged 26–30 years were 4 times more likely to use guideline than those aged >40 years. Caregivers with primary education were 4 times more likely to use guideline compared with caregivers with no formal education. Between-village variance was 0.00092 ± 0.3084. Guideline use reduced with increasing age and lower education.

Erratum to “Malaria Burden in Pregnancy at Mulago National Referral Hospital in Kampala, Uganda”

Tue, 28 Jun 2011 11:33:21 +0000

Media, Health Workers, and Policy Makers' Relationship and Their Impact on Antimalarial Policy Adoption: A Population Genetics Perspective

Mon, 20 Jun 2011 11:10:10 +0000

Drug resistance negatively impacts malaria treatments, making treatment policy revision unavoidable. So far, studies relating sociopolitical and technical issues on policy change with malaria parasite genetic change are lacking. We have quantified the effect of malaria treatment policy on drug pressure and the influence of the media, policy makers, and health worker relationship on parasite population genetic change in Kilombro/Ulanga district. Cross-sectional surveys of asymptomatic infections conducted before, during and after the switch from chloroquine to sulphadoxine/pyrimethamine were used for genetic analysis of SP resistance genes in 4,513 asymptomatic infections identified, and their frequency change was compared with retrospective study of the documented process of policy change. Highly significant changes of dhfr and dhps resistance alleles occurred within one year of switch to SP first line, followed by a decline of their rate of selection caused by reduction of SP usage, as a result of negative media reports on SP usage and lack of adequate preparations.

Mapping Malaria Transmission Risk in Northern Morocco Using Entomological and Environmental Data

Sun, 12 Jun 2011 14:58:53 +0000

Malaria resurgence risk in Morocco depends, among other factors, on environmental changes as well as the introduction of parasite carriers. The aim of this paper is to analyze the receptivity of the Loukkos area, large wetlands in Northern Morocco, to quantify and to map malaria transmission risk in this region using biological and environmental data. This risk was assessed on entomological risk basis and was mapped using environmental markers derived from satellite imagery. Maps showing spatial and temporal variations of entomological risk for Plasmodium vivax and P. falciparum were produced. Results showed this risk to be highly seasonal and much higher in rice fields than in swamps. This risk is lower for Afrotropical P. falciparum strains because of the low infectivity of Anopheles labranchiae, principal malaria vector in Morocco. However, it is very high for P. vivax mainly during summer corresponding to the rice cultivation period. Although the entomological risk is high in Loukkos region, malaria resurgence risk remains very low, because of the low vulnerability of the area.