EHP Library Malaria Bulletin, Feb 23-Mar 8, 2001

In the News

Workshop in Uganda, August 27-31, 2001

Lotte, Richard, Wenzel and Sian are in the middle of planning a research workshop in Uganda between 27-31 August 2001 about People and Malaria Medicines–this group is interested in social and economic aspects of malaria and formed a network on People and Malaria Medicines about four years ago. This will be their third workshop. If you would like to find more about this group and details about the August workshop you can send an e-mail to one or all of

Dr Richard Odoi, Makerere University Uganda e-mail [email protected]

Dr Sian Clarke, Danish Bilharziasis Laboratory
[email protected]

Dr Lotte Meinert, Institute of Anthropology
[email protected]

Dr Wenzel Geissler, Institute of Anthropology — [email protected]

Regards,
Martin Sarikiael Alilio, PhD
Multilateral Initiative on Malaria, Fogarty International Center National Institutes of Health
E-mail [email protected]

Social Sciences and Malaria

Ann Trop Paediatr 2000 Dec;20(4):273-82

Comprehensive community effectiveness of health care. A study of malaria treatment in children and adults in rural Burkina Faso.
Krause G, Sauerborn RDepartment of Tropical Hygiene and Public Health, Heidelberg University, Germany. Email: kraus[email protected]
Malaria is one of the most important causes of morbidity and mortality in children in sub-Saharan Africa, yet community effectiveness of treatment is not well understood. This study presents a quantitative estimate of community effectiveness of malaria treatment in Burkina Faso, based on population surveys, observational studies of health services and user surveys. Analysis of seven steps in the process of treating malaria reveal the following: (1) 21% of people with malaria attend health centres; (2) 31% of them have a sufficient history taken; (3) 69% receive a complete clinical examination; (4) 81% receive the correct dosage of drugs prescribed; (5) 91% purchase the drugs; (6) 68% take the drugs as prescribed; (7) the drugs are estimated to be 85% effective. Taking all the steps into account, overall community effectiveness is estimated to be 3%. Statistically significant differences in age and gender are seen in some steps. Quinine is prescribed too frequently. Critical issues in educating health care workers include complete history-taking and clinical examination, rational indication for quinine and adjusted drug dosages for children. We identify utilization and diagnostic quality as offering the greatest potential for improvement in overall community effectiveness.

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Acta Trop 2001 Feb 23;78(2):139-146

Socio-economic and environmental protective/risk factors for severe malaria in Thailand.

Nacher M, Singhasivanon P, Vannaphan S, Treeprasertsuk S, Phanumaphorn M, Traore B, Looareesuwan S, Gay F

Unite INSERM 511: Immunobiologie Cellulaire et Moleculaire des Infections Parasitaires, Faculte de medecine Pitie-Salpetriere, 91 boulevard de l’Hopital, 75634 Cedex 13, Paris, France

We conducted a cross-sectional study to identify the socio-economic and environmental protective/risk factors for severe malaria in Thailand. Forty-six cases of severe malaria, 72 cases of non-severe malaria with high parasite biomass and 40 mild malaria cases were included. When comparing severe malaria and non-severe malaria with high parasite biomass, specific logistic regression models showed a significant protective effect for helminths, adjusted odds ratio 0.24 (0.07-0.78) for low body mass index (BMI), adjusted odds ratio 0.11 (0.02-0.58). When comparing severe and mild malaria, a longer residence duration, adjusted odds ratio 0.36 (0.09-0.83) and the use of antimalarial self-medication, adjusted odds ratio 0.08 (0.009-0.84) were associated with protection from severe malaria. Using stepwise logistic regression with all the variables inserted in the model yielded similar results. These findings suggest specific immunity and self-medication control parasite multiplication whereas helminths and malnutrition more specifically affect the pathogenesis of severe malaria.

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Asia Pac J Public Health 1999;11(2):94-100

Cost analysis of malaria patients in Taikkyi Township Myanmar.
Lwin AM, Umenai T

Department of Health Policy and Planning, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan.

A hospital and clinic-based study was conducted in one malaria endemic area, Taikkyi Township, Yangon Division, Myanmar, for analysis of cost incurred by different types of malaria cases and the factors influencing the cost of illness from July to October 1995. A total of 100 patients admitted to hospital and 100 patients receiving ambulatory care from malaria clinics were interviewed using a structured questionnaire. Total cost of one episode of malaria was estimated to be kyats 559 for ambulatory care, kyats 2582 for an uncomplicated admitted case, kyats 4056 for one episode of cerebral malaria, kyats 4568 for one episode of other severe and complicated malaria and kyats 4758 for one episode of malaria with other disease. This study showed that the cost of illness for patients attending outpatient malaria clinics who received early diagnosis and prompt treatment was four to seven times cheaper than the cost of illness for hospitalized malaria cases. Multivariate analysis revealed the factors that contributed to high cost of care. Duration of illness before getting any type of treatment was the key factor that contributed to high or low cost of care. Long duration of illness before getting any type of treatment can lead to high malaria parasite density, long duration of actual illness and high total attendance cost. Therefore, it is recommended that people from malaria endemic areas should be informed to seek early treatment from health staff, and primary health care services should be made accessible to people who live in malaria endemic areas. The information obtained from this study will be useful in planning future malaria control programs and influencing policy makers to focus on timely and effective treatment of non-severe cases, which can save a large amount of economic loss due to treatment of severe malaria.

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PubMed, Feb 14 – February 22, 2001

Kidney Int 2001 Mar;59(3):1044-1051

Effects of sodium artesunate, a new antimalarial drug, on renal function.

Campos SB, Rouch LH, Seguro AC

Laboratorio de Pesquisa Basica, LIM-12, Disciplina de Nefrologia, Faculdade de Medicina USP, Sao Paulo, Brazil.

BACKGROUND: Sodium artesunate is currently used in malaria treatment. Adverse effects of this drug have not been described, probably because they cannot be differentiated from malaria-related effects. METHODS: The effects on renal function of an acute infusion of sodium artesunate (12 mg/kg body weight) were studied in the rat with clearance techniques. We also evaluate the effect of sodium artesunate on chloride lumen-bath flux (Cl Jlb) in the isolated thick ascending limb of the loop of Henle (TALH) microperfused in vitro. RESULTS: Acute infusion of artesunate to the rat decreased inulin clearance, despite an increase in renal blood flow. These effects were associated with an increase in urinary excretion of sodium, chloride, potassium, and nitric oxide metabolites (NO2/NO3). In water-loaded animals, artesunate increased sodium and water distal delivery and decreased free water clearance (CH2O) factored for sodium and water delivery. Following hypertonic NaCl infusion, artesunate decreased free water excretion (TcH2O) corrected by clearance of osmolarity (COsm). In vitro, artesunate 10-6 and 10-3 mol/L added to bath solution decreased chloride lumen-bath flux in isolated rabbit TALH in a dose-dependent manner, with the threshold effect at 10-4 mol/L. This effect was completely blocked by NG-nitroL-arginine-metilester (L-NAME) 5 mmol/L. Artesunate 10-4 mol/L added to the perfusion solution did not change Cl Jlb. CONCLUSION: These findings suggest that artesunate decreases glomerular filtration rate and increases renal blood flow and urinary excretion of Na, Cl, and K. These effects were due, at least in part, to the inhibition of Cl transport across cortical and medullary TALH, and were mediated by local production of nitric oxide, since it is associated with an increase in NO2/NO3 urinary excretion and it is blocked by L-NAME in vitro.

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Acta Trop 2001 Feb 23;78(2):155-162

Prospective risk of morbidity in relation to multiplicity of infection with Plasmodium falciparum in Sao Tome
Muller DA, Charlwood JD, Felger I, Ferreira C, do Rosario V, Smith T

Department of Public Health and Epidemiology, Swiss Tropical Institute, Socinstrasse 57, Postfach CH-4002, Basle, Switzerland

The prospective risk of acute morbidity was analysed in relation to multiplicity of Plasmodium falciparum infection in 491 individuals in a peri-urban community in Sao Tome. In an initial cross-sectional survey, 40.5% of individuals were recorded by microscopy as infected with P. falciparum, and by PCR 60.5%, with the maximum prevalence in children aged 5-10 years. PCR-RFLP typing of the msp-2 gene of P. falciparum found a mean of 2.4 parasite genotypes per infected person, with little age dependence in this multiplicity and a total of 43 different msp-2 alleles identified. None of these were unique for Sao Tome. Study participants were encouraged to report to a project worker whenever they suffered a febrile illness. During the 3 months following the parasitological survey the recorded incidence rates decreased with increasing baseline msp-2 multiplicity, both for P. falciparum-positive episodes and for fever without parasitaemia. While this is consistent with suggestions that multiple P. falciparum infections may protect against super-infecting parasites, confounding by patterns of health service usage is an alternative explanation. The incidence of clinical malaria episodes was only a little higher in children than in adults. This weak age-dependence in clinical immunity might be a consequence of a cohort effect resulting from resurgence of the disease after the breakdown of malaria control programs in the 1980s.

PMID: 11230825

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J Clin Microbiol 2001 Mar;39(3):1025-1031

Persistent ICT Malaria P.f/P.v Panmalarial and HRP2 Antigen Reactivity after Treatment of Plasmodium falciparum Malaria Is Associated with Gametocytemia and Results in False-Positive Diagnoses of Plasmodium vivax in Convalescence.Tjitra E, Suprianto S, McBroom J, Currie BJ, Anstey NM

Communicable Diseases Research Centre, National Institute of Health Research and Development, Jakarta, Indonesia.

A problem with rapid Plasmodium falciparum-specific antigen histidine-rich protein 2 (HRP2) detection tests for malaria is the persistence of antigen in blood after the disappearance of asexual-stage parasitemia and clinical symptoms, resulting in false-positive (FP) test results following treatment. The ICT P.f/P.v immunochromatographic test detects both HRP2 and a panmalarial antigen (PMA) found in both P. falciparum and Plasmodium vivax. To examine posttreatment antigen persistence with this test and whether persistent sexual-stage forms (gametocytes) are a cause of FP tests after treatment, we compared serial antigen test results with microscopy results from patients symptomatic with P. falciparum malaria in Indonesia for 28 days following treatment with chloroquine (CQ; n = 66), sulfadoxine-pyrimethamine (SP; n = 36), and artesunate plus sulfadoxine-pyrimethamine (ART + SP; n = 15). Persistent FP antigenemia following SP treatment occurred in 29% (HRP2) and 42% (PMA) of the patients on day 7 and in 10% (HRP2) and 23% (PMA) on day 14. The high rates of persistent HRP2 and PMA antigenemia following CQ and SP treatment were strongly associated with the presence of gametocytemia, with the proportion with gametocytes on day 7 posttreatment being significantly greater in those with FP results than in those with true-negative PMA and HRP2 results. Gametocyte frequency on day 14 post-SP treatment was also greater in those with FP PMA results. Following SP treatment, PMA persisted longer than HRP2, giving an FP diagnosis of P. vivax in up to 16% of patients on day 14, with all FP P. vivax diagnoses having gametocytemia. In contrast, PMA was rapidly cleared following ART + SP treatment in association with rapid clearance of gametocytemia. Gametocytes appear to be an important cause of persistent posttreatment panmalarial antigenemia in areas of endemicity and may also contribute in part to persistent HRP2 antigenemia following treatment.

PMID: 11230422

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Clin Infect Dis 2001 Mar 1;32(5):838-841

Effect of Antipyretic Drugs in Children with Malaria.
Lell B, Sovric M, Schmid D, Luckner D, Herbich K, Long HY, Graninger W, Kremsner PG

Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon; Department of Parasitology, Institute of Tropical Medicine, University of Tubingen, Tubingen, Germany; Department of Infectious Diseases, Internal Medicine I, University of Vienna, Vienna, Austria.

A comparison of different antipyretics in children with malaria showed a small effect of naproxen, but not of metamizol, on the reduction of fever peaks. Antipyretic treatment had no effect on fever clearance and therefore should be used cautiously in the treatment of malaria.

PMID: 11229858

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Trends Parasitol 2001 Feb;17(2):95-9

Malaria early warning in Kenya.
Hay SI, Rogers DJ, Shanks GD, Myers MF, Snow RW

Trypanosomiasis and Land-use in Africa (TALA) Research Group, Dept of Zoology, University of Oxford, South Parks Road, Oxford, UK OX1 3PS. Email: [email protected]

Kenya displays large spatiotemporal diversity in its climate and ecology. It follows that malaria transmission will reflect this environmental heterogeneity in both space and time. In this article, we discuss how such heterogeneity, and its epidemiological consequences, should be considered in the development of early warning systems for malaria epidemics.

PMID: 11228016

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Parasitol Int 2000 Jan;48(3):271-4

Potent in vivo antimalarial activity of 3,15-di-O-acetylbruceolide against Plasmodium berghei infection in mice.
Kim HS, Shibata Y, Ko N, Ikemoto N, Ishizuka Y, Murakami N, Sugimoto M, Kobayashi M, Wataya Y

Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan.

The antimalarial activity of the O-acylated bruceolide derivative, 3,15-di-O-acetylbruceolide, was evaluated against Plasmodium berghei in vivo. The concentration of 3,15-di-O-acetylbruceolide required for 50% suppression (ED50) of P. berghei in mice was 0.46 +/- 0.06 mg/kg/day, whereas bruceolide was only half as effective as 3,15-di-O-acetylbruceolide. Two antimalarial drugs used clinically, chloroquine and artemisinin, demonstrated only low activity corresponding to 1/4 and 1/12 of the ED50 value of 3,15-di-O-acetylbruceolide, respectively. These results may be helpful in the design of better chemotherapeutic bruceolides against falciparum malaria.

PMID: 11227768

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Sante 2000 Nov;10(6):425-433

Antimalarial drugs and their directions for use in the African environment
Zoguereh DD, Delmont J

Faculte des sciences de la sante, Bangui, Republique centrafricaine.

In the tropical African environment, malaria is both a major public health problem and a problem of socioeconomic development. It is caused by various agents, the most virulent and only lethal one of which is Plasmodium falciparum. This parasite is controlled by the appropriate use of antimalarial drugs and methods of individual and collective protection. The principal drugs used to treat bouts of malaria without vomiting caused by P. falciparum are amino-4-quinoleines, essentially chloroquine. This is based on the level of resistance of P. falciparum to drugs in most African countries, particularly those of Central and West Africa. Malawi is the only country of southern Africa to have replaced chloroquine by sulfadoxine-pyrimethamine for this indication, in 1993. In cases of bouts of benign malaria with vomiting, but that are not serious, and severe malaria caused by P. falciparum (suspected or confirmed) with or without drug resistance, quinine should be given intravenously for at least three days. Once the patient regains consciouness or the digestive problems cease, quinine treatment should be given orally for 5 to 7 days. Sulfadoxine-pyrimethamine can be given as an alternative to quinine. The other antimalarial drugs currently on the African market (halofantrine, mefloquine, artemisinine and its derivatives) are often used inappropriately and should be used only in exceptional cases of severe bouts of complicated P. falciparum malaria, with suspected or confirmed resistance to amino-4-quinoleines. Individual protection against the Anopheles mosquito, the principal vector of malaria in Africa, is based largely on the use of mosquito nets impregnated with pyrethroid insecticide and the use of aerosols. Collective protection involves essentially environment-based measures.

PMID: 11226940

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Sante 2000 Nov;10(6):389-392

The risk of malaria transmission by blood transfusion at Cotonou, Benin
Kinde-Gazard, Oke J, Gnahoui I, Massougbodji A

Parasitologie/FSS, 03BP 1428 Cotonou, Benin.

The risk of transmission of infectious agents by blood transfusion is a permanent preoccupation for diseases that we do not know how to cure, such as hepatitis B, hepatitis C and AIDS. However, few studies have been carried out concerning the risks of transmitting curable infectious diseases, such as malaria. We carried out a cross-sectional study of 355 healthy blood donors in the rainy season, in which we used thick and thin blood film smears to screen for malaria. We found that 33.5% of donors harbored trophozoites and were therefore capable of transmitting malaria via blood donation. There were 1,000 to 4,760 parasites per microliter of blood and there was no relationship between the load of parasitized red blood cells and clinical malaria. Plasmodium falciparum was the most common species identified (96.63% of cases). The results confirm that it is vital, in this age of resistance to anti-malaria drugs and HIV, to screen blood donations systematically. Patients receiving transfusions should be given anti-malaria treatment and donors should be encouraged to sleep under treated mosquito nets.

PMID: 11226934

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Microbes Infect 2001 Jan;3(1):49-59

Modulation of host responses to blood-stage malaria by interleukin-12: from therapyto adjuvant activity.
Stevenson MM, Su Z, Sam H, Mohan K

Centre for the Study of Host Resistance, McGill University and The Montreal General Hospital Research Institute, 1650 Cedar Avenue, Quebec H3G 1A4, Montreal, Canada

This review focuses on the role of interleukin (IL)-12, a proinflammatory cytokine with pleiotropic effects as a potent immunoregulatory molecule and hematopoietic growth factor, in infection with Plasmodium parasites, the causative agents of malaria. IL-12 has been demonstrated to have profound effects on the immune response to blood-stage malaria, to induce protection, and to alleviate malarial anemia. In combination with an anti-malarial drug, IL-12 is effective in an established malaria infection. This cytokine also has potent immune effects as a malaria vaccine adjuvant. However, IL-12 can also mediate pathology during blood-stage malaria.

PMID: 11226854

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Mol Biochem Parasitol 2001 Feb;112(2):253-261

The Plasmodium falciparum knob-associated PfEMP3 antigen is also expressed at pre-erythrocytic stages and induces antibodies which inhibit sporozoite invasion.
Gruner AC, Brahimi K, Eling W, Konings R, Meis J, Aikawa M, Daubersies P, Guerin-Marchand C, Mellouk S, Snounou G, Druilhe P

Unite de Parasitologie Biomedicale, Institut Pasteur, 25 and 28 Rue du Dr. Roux, Cedex 15, 75724, Paris, France

The expression of the pfemp3 gene and the corresponding PfEMP3 knob-associated protein in the pre-erythrocytic stages of Plasmodium falciparum was demonstrated by RT-PCR, Western blots, IFAT and IEM. The antigen was found on the surface of the sporozoite and in the cytoplasm of mature hepatic stage parasites. Immunological cross-reactivity was observed with sporozoites from the rodent malaria parasites Plasmodium yoelii yoelii and Plasmodium berghei and was exploited to assess a potential role of this protein at the pre-erythrocytic stages. Specific antibodies from immune individuals were found to inhibit P. yoelii yoelii and P. berghei sporozoite invasion of primary hepatocyte cultures. PfEMP3 should now be added to the small list of proteins expressed at the pre-erythrocytic stages of P. falciparum, and its vaccine potential now deserves to be investigated.

PMID: 11223132

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Mol Biochem Parasitol 2001 Feb;112(2):239-252

A bifunctional dihydrofolate synthetase-folylpolyglutamate synthetase in Plasmodium falciparum identified by functional complementation in yeast and bacteria.
Salcedo E, Cortese JF, Plowe CV, Sims PF, Hyde JE

Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology (UMIST), PO Box 88, M60 1QD, Manchester, UK

Folate metabolism in the human malaria parasite Plasmodium falciparum is an essential activity for cell growth and replication, and the target of an important class of therapeutic agents in widespread use. However, resistance to antifolate drugs is a major health problem in the developing world. To date, only two activities in this complex pathway have been targeted by antimalarials. To more fully understand the mechanisms of antifolate resistance and to identify promising targets for new chemotherapies, we have cloned genes encoding as yet uncharacterised enzymes in this pathway. By means of complementation experiments using 1-carbon metabolism mutants of both Escherichia coli and Saccharomyces cerevisiae, we demonstrate here that one of these parasite genes encodes both dihydrofolate synthetase (DHFS) and folylpolyglutamate synthetase (FPGS) activities, which catalyse the synthesis and polyglutamation of folate derivatives, respectively. The malaria parasite is the first known example of a eukaryote encoding both DHFS and FPGS activities in a single gene. DNA sequencing of this gene in antifolate-resistant strains of P. falciparum, as well as drug-inhibition assays performed on yeast and bacteria expressing PfDHFS-FPGS, indicate that current antifolate regimes do not target this enzyme. As PfDHFS-FPGS harbours two activities critical to folate metabolism, one of which has no human counterpart, this gene product offers a novel chemotherapeutic target with the potential to deliver a powerful blockage to parasite growth.

PMID: 11223131

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Mol Biochem Parasitol 2001 Feb;112(2):229-237

Anopheles gambiae laminin interacts with the P25 surface protein of Plasmodium berghei ookinetes.
Vlachou D, Lycett G, Siden-Kiamos I, Blass C, Sinden RE, Louis C

Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Vassilika Vouton, 711 10 Heraklion, Crete, Greece

Laminin is a major constituent of the basal lamina surrounding the midgut of the malaria vectors that has been implicated in the development of the Plasmodium oocyst. In this report we describe the cloning of the Anopheles gambiae gene encoding the laminin gamma1 polypeptide and follow its expression during mosquito development. To further investigate the putative role of laminin in the transmission of the malaria parasite we studied the potential binding of the P25 surface protein of Plasmodium berghei using a yeast two-hybrid system. Heterodimer formation was observed and does not require any additional protein factors since purified fusion proteins can also bind each other in vitro. Laminin gamma1 also interacts with the paralogue of P25, namely P28, albeit more weakly, possibly explaining why the two parasite proteins can substitute for each other in deletion mutants. This represents the first direct evidence for molecular interactions between a surface protein of the Plasmodium parasite with an Anopheles protein; the strong interplay between laminin gamma1 and P25 suggests that this pair of proteins may function as a receptor/ligand complex regulating parasite development in the mosquito vector.

PMID: 11223130

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Mol Biochem Parasitol 2001 Feb;112(2):219-228

The malaria parasite Plasmodium falciparum possesses a functional thioredoxin system.
Krnajski Z, Gilberger T, Walter RD, Muller S

Bernhard Nocht Institute for Tropical Medicine, Biochemical Parasitology, Bernhard-Nocht-Strasse 74, 20359, Hamburg, Germany

The thioredoxin system consists of the NADPH dependent disulphide oxidoreductase thioredoxin reductase (TrxR) which catalyses the reduction of the small protein thioredoxin. This system is involved in a variety of biological reactions including the reduction of deoxyribonucleotides, transcription factors and hydrogen peroxide. In recent years the TrxR of the malaria parasite Plasmodium falciparum was isolated and characterised using model substrates like 5,5′-dithiobis (2-nitrobenzoic acid) (DTNB) and Escherichia coli thioredoxin. Here we report on the isolation of a cDNA encoding for P. falciparum thioredoxin (PfTrx) and the expression and characterisation of the recombinant protein, the natural substrate of PfTrxR. The deduced amino acid sequence of PfTrx encodes for a polypeptide of 11715 Da and possesses the typical thioredoxin active site motif CysGlyProCys. Both cysteine residues are essential for catalytic activity of the protein, as shown by mutational analyses. Steady state kinetic analyses with PfTrxR and PfTrx in several coupled assay systems resulted in K(m)-values for PfTrx in the range of 0.8-2.1 ?M which is about 250-fold lower than for the model substrate E. coli thioredoxin. Since the turnover of both substrates is similar, the catalytic efficiency of PfTrxR to reduce the isolated PfTrx is at least 250-fold higher than to reduce E. coli thioredoxin. PfTrx contains a cysteine residue in position 43 in addition to the active-site cysteine residues, which is partially responsible for dimer formation of the protein as demonstrated by changing this amino acid into an alanine residue. Using DTNB we showed that all three cysteine residues present in PfTrx are accessible to modification by this compound. Surprisingly the first cysteine residue of the active site motif (Cys30) is less accessible than the second cysteine (Cys33), which is highly prone to the modification. These results suggest a difference in the structure and reaction mechanism of PfTrx compared to other known thioredoxins.PMID: 11223129

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Mol Biochem Parasitol 2001 Feb;112(2):211-218

Rapid recombination among transfected plasmids, chimeric episome formation and trans gene expression in Plasmodium falciparum.
Kadekoppala M, Cheresh P, Catron D, Ji D, Deitsch K, Wellems TE, Seifert HS, Haldar K

Department of Pathology, Northwestern University Medical School, 303 E. Chicago Ave., 60611-3008, Chicago, IL, USA

Although recombination is known to be important to generating diversity in the human malaria parasite P. falciparum, the low efficiencies of transfection and the fact that integration of transfected DNA into chromosomes is observed only after long periods (typically 12 weeks or more) have made it difficult to genetically manipulate the blood stages of this major human pathogen. Here we show that co-transfection of a P. falciparum line with two plasmids, one expressing a green fluorescent protein (gfp) reporter and the other expressing a drug resistance marker (Tgdhfr-ts M23), allowed selection of a population in which about approximately 30% of the parasites produce GFP. In these GFP-producing parasites, the transfected plasmids had recombined into chimeric episomes as large as 20 kb and could be maintained under drug pressure for at least 16 weeks. Our data suggest that chimera formation occurs early (detected by 7-14 days) and that it involves homologous recombination favored by presence of the same P. falciparum 5’hrp3 UTR promoting transcription from each plasmid. This indicates the presence of high levels of homologous recombination activity in blood stage parasites that can be used to drive rapid recombination of newly introduced DNA, study mechanisms of recombination, and introduce genes for trans expression in P. falciparum.

PMID: 11223128

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Ann Trop Paediatr 2000 Dec;20(4):265-71

Independent indicators of outcome in severe paediatric malaria: maternal education, acidotic breathing and convulsions on admission.
Varandas L, Julien M, Van Lerberghe W, Goncalves L, Ferrinho P

Centro de Malaria e de Outras Doencas Tropicais and Health Systems Unit, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal. Email: [email protected]

Severe malaria is an important cause of death in hospitalized children in Mozambique, but the risk factors for this remain unclear. The objectives of the study were to define simple clinical criteria to identify on admission the children most at risk of dying. We studied prospectively 559 children admitted with severe malaria to the Department of Paediatrics of the Central Hospital of Maputo, Mozambique between March 1995 and August 1996. The case fatality rate was 3.6%. In a multiple logistic regression model, mothers’ education (RR = 9.6, 95% CI 1.2-76.0), acidotic breathing (RR = 4.3, 95% CI 1.3-13.8) and convulsions in the emergency room (RR = 8.1, 95% CI 2.6-25.1) were associated with outcome. Together they predicted 97% of outcomes but only 33.3% of deaths.

PMID: 11219163

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J Vector Ecol 2000 Dec;25(2):203-11

Plasmodium vivax polymorphs and Plasmodium falciparum circumsporozoite proteins in Anopheles (Diptera: Culicidae) from Belize, Central America.

Achee NL, Korves CT, Bangs MJ, Rejmankova E, Lege M, Curtin D, Lenares H, Alonzo Y, Andre RG, Roberts DR

Uniformed Services University of the Health Sciences, Department of Preventive Medicine and Biometrics, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA.

Eight species of Anopheles mosquitoes from indoor/outdoor human landing collections in Belize, Central America, were examined for human Plasmodium circumsporozoite protein (CSP) using an enzyme-linked immunosorbent assay (ELISA). A total of 14 of 9,104 females tested were positive from general surveys throughout Belize and three of 11,966 were positive from a longitudinal study in Caledonia, northern Belize. ELISA results, using pooled head-thorax preparations and species-specific monoclonal antibodies directed against the circumsporozoite proteins of Plasmodium falciparum and two Plasmodium vivax polymorphs (210 and VK247), found four species reactive: Anopheles vestitipennis (3 pools), Anopheles darlingi (2 pools), Anopheles albimanus (10 pools), and Anopheles gabaldoni (2 pools). The minimum field infection rates (MFIR) for combined Plasmodium species from the general survey were 0.282% for An. vestitipennis, 0.271% for An. darlingi, 0.126% for An. albimanus, and 0.395% for An. gabaldoni. MFIRs for combined Plasmodium species from the longitudinal study in the village of Caledonia were 0.018% for both An. vestitipennis and An. albimanus and 1.66% for An. gabaldoni. Positive CSP pools were collected from the Cayo, Corozal, Orange Walk, Stann Creek, and Toledo political districts. No CSP positive pools were detected from collections in the Belize District. The study provides valuable information on the spatial distribution and species type of Plasmodium positive mosquitoes. This information, in combination with other vector data, suggest that An. vestitipennis and An. darlingi are commonly involved in malaria transmission. Additionally, these species appear to be much more efficient vectors than An. albimanus in Belize.

PMID: 11217218

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Ann Trop Med Parasitol 2000 Dec;94(8):771-8

Incidence and management of malaria in two communities of different socio-economic level, in Accra, Ghana.
Biritwum RB, Welbeck J, Barnish G

Department of Community Health, Ghana Medical School, Korle Bu, Accra, Ghana. Email: [email protected]


Two adjacent communities of differing socio-economic levels were selected, in Accra, Ghana, for the study of the home management of malaria. The youngest child in each selected household, each of which had a child aged < 5 years, was recruited for weekly follow-up, following informed consent. Malaria was the most common condition reported by the ‘caregivers’ (mothers of the subjects and others caring for the subjects) in each community, with 2.0 episodes of clinical malaria/child during the 9-month study. Most (89%) of the caregivers in the better-off community had been educated beyond primary-school level, but 55% of the caregivers in the poorer community had either received no formal education or only primary-school education. This difference was also reflected by the educational facilities provided to the children studied: 52% of the those in the better-off community attended nurseries, kindergartens or creches, compared with 8% of the children investigated in the poorer community. The proportion of caregivers who purchased drugs without prescription or used left-over drugs to treat clinical malaria in the children was higher in the poorer community (82% v. 53%), and a child from the poorer community was less likely to have been taken to a clinic or hospital to be treated for malaria than a child from the better-off community (27% v. 42%). During the follow-up period two children died, one from each community. Treatment of malaria in young children is likely to be less effective in the poorer community, where a lack of economic access to health services was demonstrated.

PMID: 11214095

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Ann Trop Med Parasitol 2000 Dec;94(8):759-68; discussion 769-70

Chloroquine prophylaxis, iron/folic-acid supplementation or case management of malaria attacks in primigravidae in western Uganda: effects on congenital malaria and infant haemoglobin concentrations.
Ndyomugyenyi R, Magnussen P

Ministry of Health, Vector Control Division, Kampala, Uganda.

A randomized, double-blind, placebo-controlled trial, which compared the effects of three interventions (weekly chloroquine prophylaxis, daily iron and weekly folic-acid supplementation, and case management of malaria) on congenital malaria, maternal haemoglobin (Hb) and foetal outcome, was conducted among primigravidae resident in Hoima district, Uganda. Among 473 babies examined at birth or within 7 days of birth, 198 (42%) were parasitaemic, the level of parasitaemia in an infant being strongly correlated with those of placental (P< 0.01) and maternal, peripheral parasitaemia (P < 0.01). However, 33 (17%) of the parasitaemic babies were born to mothers who had placental but not peripheral parasitaemia, 22 (11%) to mothers who had peripheral but not placental parasitaemia, and 12 (6%) to mothers with neither peripheral nor placental parasitaemia. Overall, 163 babies were each examined for malarial parasites at birth and 1 month later. Of the 76 (47%) found to have parasitaemia at birth, 37 (23%) appeared aparasitaemic at the 1-month follow-up but 28 (17%) were still parasitaemic at that time. Among the babies born to the mothers who only received case management of malaria during pregnancy, parasitaemia at birth was associated with infant anaemia at birth (i.e. < 140 g Hb/litre; P = 0.03). Infants found to be parasitaemic at the 1-month follow-up had lower mean concentrations of Hb at that time than their aparasitaemic counterparts (P= 0.03). Parasitaemia at birth was not significantly associated with low birthweight, in any of three intervention groups. The intervention given to the mother had no significant effect on the parasitaemia of her baby, either at birth or at the age of 1 month. Congenital malaria per se may have little influence on birthweight but may have an impact on infant anaemia. In conclusion, congenital parasitaemia was not associated with birthweight, but was related to anaemia at birth in infants born to women who had only received active case management during their pregnancies.

PMID: 11214094

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Ann Trop Med Parasitol 2000 Dec;94(8):749-58

In-vivo sensitivity of Plasmodium vivax isolates from Rond nia (western Amazon region, Brazil) to regimens including chloroquine and primaquine.
Villalobos-Salcedo JM, Tada MS, Kimura E, Menezes MJ, Pereira da Silva LH

Centro de Pesquisa em Medicina Tropical, Rond nia, Brazil. Email: [email protected]

Seventy-nine adults with Plasmodium vivax malaria, from the Porto Velho area of Rond nia (western Amazon region, Brazil), gave informed consent to participate in a blind, clinical study of two regimens of treatment with chloroquine (CQ) and primaquine. The effectiveness of the ‘classical’ regimen (CQ for 3 days, followed by primaquine for 14 days) was compared with that of a ‘short’ regimen in which the two drugs were given simultaneously for 5 days. There were no cases of recrudescence indicative of CQ resistance (i.e. within 30 days of the first treatment dose) among the 73 patients who each completed a full, supervised course of treatment. However, 10 cases of apparent relapse were observed (all > 60 days after first treatment dose), representing 6.5% (2/31) of the patients who completed 60 days of follow-up after the classical treatment and 26.7% (8/30) of the short-regimen patients who completed the same period of follow-up. PCR-based comparison of parasitic DNA collected pre- and post-treatment was successful for eight of the 10 cases of apparent relapse and indicated that two such cases, both given the short regimen of treatment, were, in fact, probable cases of re-infection rather than of relapse. The results indicate that the classical schedule of treatment with chloroquine and primaquine was more effective at preventing relapses than the short regimen. However, since prolonged treatment with primaquine often produces side-effects that are severe enough to reduce compliance, the short schedule could be a useful alternative for malaria control in endemic areas of the Amazon region.

PMID: 11214093

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Trop Doct 2001 Jan;31(1):26-7

Associated morbidities in children with sickle-cell anaemia presenting with severe anaemia in a malarious area.
Ambe JP, Fatunde JO, Sodeinde OO

Department of Paediatrics, College of Medical Sciences, University of Maiduguri, Borno State, Nigeria.

A prospective study of 104 consecutive cases of patients with sickle-cell anaemia (SCA) presenting with severe anaemia (packed cell volume < or = 15%) was carried out in the Children’s Emergency Ward of the University College Hospital, Ibadan, in 1991. The patients were classified according to the type of anaemic crisis, by physical findings, serum bilirubin and reticulocyte counts. Other investigations included a blood film for malaria parasites, blood culture, radiological investigation and lumbar puncture when necessary. The most common problems associated with SCA patients in anaemic crisis were malaria and bacterial infections–68 (66%) and 18 (17.3%) of cases, respectively. Acute chest syndrome was significantly more frequent in patients with hyperhaemolytic and acute splenic sequestration crisis compared with aplastic crisis (P < 0.05). Conjugated hyperbilirubinaemia was also significantly more frequent among patients with hyperhaemolytic crisis compared with all other anaemic crises (chi2 = 13.18, P = 0.001). The overall case fatality was 86.5/1,000 SCAs, with no fatalities in those with aplastic crisis.There were complications in six of the nine mortalities. Co-existing bacterial infections and conjugated hyperbilirubinaemia were associated with increased morbidity and mortality in patients with anaemic crisis. Patients with SCA crisis should have early evaluation and prompt treatment for associated infections.

PMID: 11205596

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Trop Doct 2001 Jan;31(1):19-21

Field trial of the RTM dipstick method for the rapid diagnosis of malaria based on the detection of Plasmodium falciparum HRP-2 antigen in whole blood.

Wolday D, Balcha F, Fessehaye G, Birku Y, Shepherd A

Microbiology Laboratory, Black Lion Hospital, Addis Abada, Ethiopia. Email: [email protected]

The performance of the Quorum RapidTest Malaria (RTM) dipstick method that detects Plasmodium falciparum histidine-rich protein-2 (PfHRP-2) antigen in whole blood was evaluated in a malaria endemic area. Results were compared with conventional Giemsa-stained blood films. Of 306 people tested 37.9% (116/306) were found to be parasitaemic; of these 66.4% (77/116) were P. vivax and 32.8% (38/116) were P. falciparum infections. There was only one (0.9%) mixed P. falciparum plus P. vivax infection.The RTM test was positive in 35/36 patients with P. falciparum identified on blood smear examination, resulting in a sensitivity of 97.2% [95% confidence interval (CI): 91.6-102.8%]. Specificity was 96.3% (95% CI: 93.9-98.6%).The RTM test had a positive predictive value of 77.8% (95% CI: 65.7-89.9%) and a negative predictive value of 99.6% (95% CI: 98.4-100.8%). Of the 10 false positives, seven reported recent malaria episode and treatment, indicating persistence of antigenaemia. If these were assumed truly infected, the positive predictive value is increased to 93.3% (95% CI: 85.8-100.8%).The RTM test was positive in all seven P. falciparum infections with gametocytes and one mixed infection, but was negative in all falciparum gametocytes and relapsing fever cases. All but one P. vivax infection gave negative result on the RTM test.The RTM test missed one patient with parasitaemia. The test is highly sensitive and specific requiring no instrument or trained personnel. It appears to be a very useful tool for rapid diagnosis of malaria, especially in the rural health institutions with limited diagnostic facilities.

PMID: 11205592

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J Am Mosq Control Assoc 2000 Dec;16(4):331-8

Insecticide susceptibility in Anopheles pseudopunctipennis from Colombia: comparison between bioassays and biochemical assays.
Ocampo CB, Brogdon WG, Orrego CM, Toro G, Montoya-Lerma J

Centro Internacional de Entrenamiento e Investigaciones Medicas, Cali, Colombia.

Anopheles pseudopunctipennis, one of the primary vectors of malaria in the southwest of Colombia, was evaluated for susceptibility to the 3 major insecticide groups (organophosphates, pyrethroids, and carbamates) by bioassay and biochemical assay. Larval populations, which were collected principally from irrigation channels in agricultural areas, where the intensity of insecticide use varied, were utilized to establish susceptibility for the 1st time in this species. The baselines for each population showed a range of biological susceptibility to the insecticides evaluated, but overall no resistance was detected according to standards established by the World Health Organization. The high sensitivity of biochemical microassays enabled the detection of a small proportion of mosquitoes with higher levels of nonspecific esterases and mixed-function oxidases from 2 areas where agricultural application of organophosphate and pyrethroid insecticides had been heavy. These differences were not sufficient to affect susceptibility as measured by bioassay. No evidence of insensitive acetylcholinesterase was observed. Absence of resistance in areas that have experienced heavy insecticide application could be explained by genetic drift, by gene flow from areas without insecticide pressure, by manner of exposure to the insecticides, or by recent changes in agricultural activities that decreased insecticide use. Baseline values were established that serve as provisional susceptibility thresholds for applying simple Centers for Disease Control and Prevention biochemical assay and bioassay methods to larvae of this anopheline species.

PMID: 11198920

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J Am Mosq Control Assoc 2000 Dec;16(4):295-312

Mosquito vector control and biology in Latin America–a tenth symposium.
The 10th annual Latin American symposium presented by the American Mosquito Control Association (AMCA) was held as part of the 66th Annual Meeting in Atlantic City, NJ, in March 2000. The principal objective, as for the previous 9 symposia, was to promote participation in the AMCA by vector control specialists, public health workers, and academicians from Latin America. This publication includes summaries of 57 presentations that were given orally in Spanish or presented as posters by participants from 9 countries in Latin America. Topics addressed in the symposium included results from chemical and biological control programs and studies; studies of insecticide resistance; and molecular, ecological, and behavioral studies of vectors of dengue (Aedes aegypti). malaria (Anopheles albimanus and Anopheles aquasalis). leishmaniasis (Lutzomyia), and Chagas’ disease (Triatoma). Related topics included biology and control of scorpions and Chironomus plumosus.

PMID: 11198916

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J Am Mosq Control Assoc 2000 Dec;16(4):279-87

Anopheline ecology and malaria transmission at a new irrigation project area (Bargi Dam) in Jabalpur (Central India).
Singh N, Mishra AK

Malaria Research Centre (Field Station), Medical College Building, Jabalpur, India.

Anopheline ecology and malaria transmission were studied in a newly irrigated area of the Bargi Project, District Jabalpur, Madhya Pradesh, Central India. Observations were made for 2 years (1993-95) in 10 villages along the Bargi irrigation canal, which are situated between 44 km (head end of canal) and 78 km (tail end of canal) from the dam site. Anopheles annularis was the predominant species in the head-end villages and its abundance was directly related to the opening of the canal, whereas Anopheles culicifacies was the most abundant species in tail-end villages, where irrigation is limited. Anopheles culicifacies showed 2 typical peaks not related to canal irrigation. Site-related differences in species prevalence were significant in both immatures and adults. Malaria infection was due to Plasmodium vivax and Plasmodium falciparum. The annual parasite incidence in children and adults was significantly higher in head-end villages (>4-fold) as compared to that in tail-end villages. However, seasonal trends in the prevalence of P. falciparum and P. vivax were the same in each group, with some fluctuations. In this study, preliminary results of the investigation are presented, demonstrating the trends in anopheline ecology and parasite prevalence in relation to the dynamics of irrigation development.

PMID: 11198914

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J Commun Dis 2000 Jun;32(2):95-9

Anthropophily of Anophelines in Duars of West Bengal and other regions of India.
Nandi J, Kaul SM, Sharma SN, Lal S

Attempts have been made to identify the source of blood meals of twenty three anopheline species from various areas of high malaria endemicity in India. Anopheles minimus, Anopheles fluviatilis and Anopheles dirus showed a high propensity for human blood in North-Eastern parts of the country while Anopheles sundicus was found to be anthropophilic in Andaman & Nicobar Islands. Anopheles culicifacies, Anopheles maculatus and Anopheles philippinensis were found primarily zoophilic in north-eastern areas. High anthropophily has been closely related to sporozoite infection in anophelines specially in Anopheles minimus and is of great epidemiological significance.

PMID: 11198404

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J Commun Dis 2000 Jun;32(2):137-43

Efficacy of chloroquine in febrile Plasmodium falciparum infected children in Mewat region of Haryana.
Nandi J, Sharma SN

During 1996, Mewat region of Gurgaon district in Haryana experienced high incidence of Plasmodium falciparum malaria, assuming epidemic proportion in large number of villages affected by floods. Mortality due to fever was also high. In vivo 7 days study amongst 32 febrile P. falciparum infected children of 1 to 14 years age group in flood affected villages of Ferozpur Jhirka Community Health Centre of Mewat region was carried out. All the 32 cases showed good response to chloroquine suggesting that drug was effective and useful as first line of treatment, reducing severity of P. falciparum infection and resolving fever due to infection of the species. The study also indicated that chloroquine was an effective drug in controlling epidemic situation and mortality in areas of high incidence of P. falciparum. Pyrogenic stimulus was variable among different developmental stages of P. falciparum and suggestive of the need of earliest possible initiation of anti-malaria treatment, community based fever survey and blood smear examination. Increase in incidence of fever in an endemic community, particularly in children, should be considered as an indicator of impending outbreak of P. falciparum malaria. Effectiveness of diagnostic and control measures taken can be evaluated on the basis of incidence of malaria particularly due to P. falciparum infection and also incidence of fever in an endemic community.

PMID: 11198399

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J Commun Dis 2000 Jun;32(2):129-35

Role of macrophages in experimental malaria: VII–studies on adoptive transfer of macrophages.
Pillai CR, Devi CU

Malaria Research Centre (ICMR), 52-Nanak Enclave, Radio Colony, Delhi-110 009.

Adoptive transfer of purified macrophages harvested from normal, Plasmodium berghei infected and latent/cured mice and also macrophages exposed to parasites in vitro were carried out to see the role of macrophages in transferring immunity against P. berghei infection. Macrophages obtained from mice having high parasitaemia at a dose of one million cells/animal showed significant increase in survival period (SP) and K values, compared to controls. Macrophages exposed to low parasite density conferred significant K values only. There was a decrease in prepatent period (PP) in the animal which received macrophages from animals cured 7-11 months compared to controls. The adoptive transfer studies with macrophages conditioned in vitro to parasite contributed towards increased protection of host against P. berghei as expressed by K values only. These studies showed that the macrophages harvested from infected mice were capable of acting as immunogen against P. berghei infection.

PMID: 11198398

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J Egypt Soc Parasitol 2000 Dec;30(3):761-4

Preliminary observations on cross-mating of the malaria vector, Anopheles sergentii from two Egyptian oases.
Kenawy MA, Sowilem MM, Abdel-Hamid YM, Wahba MM

Department of Entomology, Faculty of Science, Ain Shams University, Cairo 11566, Egypt.

Intra- and inter-strain crosses were made between randomly collected adults Anopheles sergentii originated from Tersa village (El-Faiyum Governorate) and Siwa oasis (Matruh Governorate). The success of such crosses and their effects on fecundity and fertility of the parental females and on survival and development velocities of the F1 immatures were examined. No overall heterosis effects on such attributes were detected suggesting absence of genetic differences between the vector populations in these two malarious areas.

PMID: 11198374

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J Parasitol 2000 Dec;86(6):1345-8

Susceptibility of species A, B, and C of Anopheles culicifacies complex to Plasmodium yoelii yoelii and Plasmodium vinckei petteri infections.
Kaur S, Singh OP, Adak T

Malaria Research Center (ICMR), Delhi, India.

The comparative susceptibilities of colonized species A, B, and C of Anopheles culicifacies complex and Anopheles stephensi were determined for 2 rodent malaria parasites Plasmodium vinckei petteri and Plasmodium yoelii yoelii. All the 3 members of the complex were found to support complete sporogony with varying success. Controls, A. stephensi, become readily infected, with >70% developing oocysts. Of the test groups, species A had the highest percentage of mosquitoes with oocysts (>25%) and sporozoites (>15%). Anopheles culicifacies species B were least susceptible; less than 10% had oocysts and sporozoites in the salivary glands. The results demonstrate that A. culicifacies species A is most susceptible and species B is least susceptible to infections with both the parasites.

PMID: 11191914

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J Pak Med Assoc 2000 Dec;50(12):401-5

Prevalence of plasmodium slide positivity among the children treated for malaria, Jhangara, Sindh.
Hozhabri S, Akhtar S, Rahbar MH, Luby SP

Department of Community Health Sciences, Aga Khan University, Stadium Road, Karachi.

OBJECTIVE: The aim of the study was to estimate the prevalence of malaria amongst the children with fever or history of fever. SETTING: Rural Health Centre (RHC), Jhangara, a town near the Manchhar Lake in Taluka Sehwan, District Dadu, Sindh. SUBJECTS: Four hundred and thirty eight children of 6 months to 10 years of age, who attended above described RHC during August through October 1997. METHODS: A Sindhi-translated standard questionnaire was used to record symptoms and duration of child’s illness. Each child was physically examined, had their axillary temperature measured; and blood samples were collected from which Giemsa stained thick and thin blood films were examined for presence of Plasmodium parasites. RESULTS: The median age of the studied children was 24 months and 57% (250/438) were boys. Fifty three percent (231) of the study subjects were from Jhangara Town, 40% (177) and 7% (30) came from other villages and villages near to the Manchhar Lake respectively. The prevalence of Plasmodium slide positivity was 5.9% (26/438). Among Plasmodium slide positive children, 65% (17/26) were positive for P. falciparum and 35% (9/26) for P. vivax. Among the P. falciparum positive children, 88% (15/26) had scanty (MP, 1-10/100 fields) and 12% (2/26) had moderate density (MP, 10-100/100 fields) of infection. Seventeen percent (6/30) of the children from villages close to Manchhar Lake were Plasmodium slide positive compared to 7% (17/53) and 3% (5/177) from Jhangara town and other villages respectively. Cough, diarrhea, abdominal distention and vomiting were the commonly reported symptoms among the children of all ages at the time of interview. Guardians reported fever as part of the illness in all children, although during physical examination only 128 (29%) had axillary temperature > or = 37.5 degrees C. Pallor as an indicator for anemia, rash and prickly heat were the major recorded observations. CONCLUSION: The Prevalence of Plasmodium positivity was higher in children who attended from villages close to Manchhar lake, therefore especial measure needs to be considered for this area. In addition, the health care workers in rural Sindh need to adopt appropriate guidelines to differentiate the clinical malarial patients from patients with other potential infectious diseases, which may need other treatment.
PMID: 11191438

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Arch Dis Child 2001 Mar;84(3):247-253

Electroencephalographic and clinical features of cerebral malaria.
Crawley J, Smith S, Muthinji P, Marsh K, Kirkham F

KEMRI Centre for Geographic Medicine Research (Coast), Kilifi, Kenya.

BACKGROUND: Seizures are a prominent feature of childhood cerebral malaria, and are associated with an increased risk of death and neurological sequelae. We present the electroencephalographic (EEG) findings from a detailed clinical and electrophysiological study. METHODS: Children with cerebral malaria had EEGs recorded within six hours of admission, and at 12 hourly intervals until recovery of consciousness. Ten deeply comatose children underwent intracranial pressure monitoring. Children were not mechanically ventilated, which made it possible to directly correlate the clinical and EEG findings. RESULTS: Of 65 children aged 9 months and above, 40 had one or more seizures, and 18 had an episode of status epilepticus. Most seizures were partial motor, and spike wave activity consistently arose from the posterior temporo-parietal region, a border zone area lying between territories supplied by the carotid and vertebrobasilar circulations. Fifteen children had seizures that were clinically subtle or electrographic. Clinical seizures were associated with an abrupt rise in intracranial pressure. Fifty children recovered fully, seven died, and eight had persistent neurological sequelae. Initial EEG recordings of very slow frequency, or with background asymmetry, burst suppression, or interictal discharges, were associated with an adverse outcome. CONCLUSIONS: Serial EEG recording has uncovered a range of clinical, subtle, and electrographic seizures complicating childhood cerebral malaria, and has emphasised their importance in the pathogenesis of coma. Further work is required to determine the most appropriate regimen for the prophylaxis and treatment of seizures in cerebral malaria, in order to improve outcome.