EHP Library Malaria Bulletin No. 31:  Feb 19-28, 2002

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Social Sciences/Environmental Management

Soc Sci Med 2002 Feb;54(4):519-27

Altruistic willingness to pay in community-based sales of insecticide-treated nets exists in Nigeria.

Onwujekwe O, Chima R, Shu E, Nwagbo D, Akpala C, Okonkwo P.

Department of Pharmacology and Therapeutics, College of Medicine, University of Nigeria. 
Eamil: [email protected]

The objective of this study was to determine whether households who are willing to pay for insecticide-treated nets (ITNs) for themselves are prepared to contribute for the ITNs to be purchased for the indigent community members who cannot afford the nets. This was in the framework of community-based and directed sales for ITNs. The study was conducted in four malaria holoendemic communities in south-eastern Nigeria. Contingent valuation method was used to determine the altruistic willingness to pay (WTP) from randomly selected household heads or their representatives, which was elicited using an open-ended question. Theoretical validity was assessed using the Tobit model. Median altruistic WTP ranged from $0.11 to $0.21 across the four communities (95 Naira = $1). However, using a pooled data from the four communities, the mean was $0.34. In Tobit estimation, altruistic WTP varied significantly with two of the communities; the respondents were resident in, sex, marital status and the amount of savings of the respondent. It also varied significantly with the respondents’ WTP for their own ITNs and average monthly household expenditures to treat malaria (p<0.05). Altruistic WTP will exist in community-based and directed sales of ITNs. Thus there can be intra-community subsidisation by the rich for the poor who may not be able to pay for the nets. Community mobilisation and sensitisation should be used to encourage able households to actually pay at least the amounts they have stated.

S Afr Med J 2001 Nov;91(11):978-83

Malaria control–two years’ use of insecticide-treated bednets compared with insecticide house spraying in KwaZulu-Natal.

Mnzava AE, Sharp BL, Mthembu DJ, le Sueur D, Dlamini SS, Gumede JK, Kleinschmidt I.

Malaria Research Lead Programme, South African Medical Research Council, Durban.

OBJECTIVES: The objective of this study was to produce data indicating whether insecticide-treated bednets should replace insecticide house spraying as a malaria control method in South Africa. We report 2 years of preliminary data on malaria incidence comparing areas receiving insecticide-treated bednets and those subjected to house spraying in northern KwaZulu-Natal. DESIGN, SETTING AND SUBJECTS: In order to measure significant reductions in malaria incidence between the two interventions, a geographical information system (GIS) was used to identify and create seven pairs of geographical blocks (areas) in the malaria high-risk areas of Ndumu and Makanis in Ingwavuma magisterial district, KwaZulu-Natal. Individual blocks were then randomly allocated to either insecticide-treated bednets or house spraying with deltamethrin. Malaria cases were either routinely recorded by surveillance agents at home or were reported to the nearest health facility. RESULTS AND CONCLUSIONS: The results show that 2 years’ use of insecticide-treated bednets by communities in Ndumu and Makanis, KwaZulu-Natal, significantly reduced the malaria incidence both in 1997 (rate ratio (RR) = 0.879, 95% confidence interval (CI) 0.80-0.95, P = 0.04) and in 1998 (RR = 0.667, CI 0.61-0.72, P = 0.0001). Using a t-test, these significant reductions were further confirmed by an assessment of the rate of change between 1996 and 1998, showing a 16% reduction in malaria incidence in blocks using treated bednets and an increase of 45% in sprayed areas (t = 2.534, P = 0.026 (12 df)). In order to decide whether bednets should replace house spraying in South Africa, we need more data on the efficacy of treated bednets, their long-term acceptability and the cost of the two interventions.


EMBO J 2002 Mar 1;21(5):1231-1239

A genetic screen for improved plasmid segregation reveals a role for Rep20 in the interaction of Plasmodium falciparum chromosomes.

O’Donnell RA, Freitas-Junior LH, Preiser PR, Williamson DH, Duraisingh M, McElwain TF, Scherf A, Cowman AF, Crabb BS.

The Walter & Eliza Hall Institute of Medical Research, Victoria 3050, Department of Microbiology & Immunology and the Cooperative Research Centre for Vaccine Technology, The University of Melbourne, Victoria 3010, Australia, Unite de Biologie des Interactions Hote-Parasite, CNRS URA 1960, Institut Pasteur, F-75724 Paris Cedex 15, France, National Institute of Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK and Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040.
Email: [email protected]

Bacterial plasmids introduced into the human malaria parasite Plasmodium falciparum replicate well but are poorly segregated during mitosis. In this paper, we screened a random P.falciparum genomic library in order to identify sequences that overcome this segregation defect. Using this approach, we selected for parasites that harbor a unique 21 bp repeat sequence known as Rep20. Rep20 is one of six different repeats found in the subtelomeric regions of all P.falciparum chromosomes but which is not found in other eukaryotes or in other plasmodia. Using a number of approaches, we demonstrate that Rep20 sequences lead to dramatically improved episomal maintenance by promoting plasmid segregation between daughter merozoites. We show that Rep20(+), but not Rep20(–), plasmids co-localize with terminal chromosomal clusters, indicating that Rep20 mediates plasmid tethering to chromosomes, a mechanism that explains the improved segregation phenotype. This study implicates a direct role for Rep20 in the physical association of chromosome ends, which is a process that facilitates the generation of diversity in the terminally located P.falciparum virulence genes.r]

J Infect Dis 2002 Mar 1;185(5):657-664

Merozoite Surface Protein 3 and Protection against Malaria in Aotus nancymai Monkeys.

Hisaeda H, Saul A, Reece JJ, Kennedy MC, Long CA, Miller LH, Stowers AW.

Malaria Vaccine Development Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA and Department of Parasitology and Immunology, University of Tokushima School of Medicine, Tokushima, Japan.

A blood-stage vaccine based on Plasmodium falciparum merozoite surface protein 3 (MSP3) was tested for efficacy in a primate model. Aotus nancymai monkeys were vaccinated with yeast-expressed MSP3 before a lethal challenge with Plasmodium falciparum parasites. Five of 7 control monkeys had acute infections and required treatment to control parasitemia. Only 1 of 7 monkeys vaccinated with MSP3 required this treatment. The efficacy of the MSP3 vaccination appeared to be comparable to that of MSP1(42), a leading asexual vaccine candidate, in response to which 2 monkeys experienced acute infections. In the MSP3-vaccinated group, protection correlated with prechallenge titers of antibody to MSP3. In the MSP1 and control groups, protection correlated with antibody to MSP3 raised by challenge infection.

J Infect Dis 2002 Mar 1;185(5):650-6

The clinical significance of cerebrospinal fluid levels of kynurenine pathway metabolites and lactate in severe malaria.

Medana IM, Hien TT, Day NP, Phu NH, Mai NT, Van Chu’ong L, Chau TT, Taylor A, Salahifar H, Stocker R, Smythe G, Turner GD, Farrar J, White NJ, Hunt NH.

Nuffield Department of Clinical Laboratory Sciences, Oxford-Wellcome Centre for Tropical and Infectious Diseases, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. 
Email: [email protected]

A retrospective study of 261 Vietnamese adults with severe malaria was conducted to determine the relationship between cerebrospinal fluid (CSF) levels of metabolites of the kynurenine pathway, the incidence of neurologic complications, and the disease outcome. Three metabolites were measured: the excitotoxin quinolinic acid (QA); the protective receptor antagonist kynurenic acid (KA); and the proinflammatory mediator picolinic acid (PA). These measurements were related prospectively to CSF lactate levels. QA and PA levels were elevated, compared with those of controls. There was no difference in the levels of KA between these groups. Although >40% of malaria patients had QA CSF concentrations in the micromolar range, there was no association with convulsions or depth of coma. Levels of QA and PA were associated significantly with death, but a multivariate analysis suggested that these elevations were a consequence of impaired renal function. CSF lactate remained an independent and significant predictor of poor outcome.

Apoptosis 2002 Apr;7(2):91-8

Thrombocytopenia in an animal model of malaria is associated with an increased caspase-mediated death of thrombocytes.

Piguet PF, Kan CD, Vesin C.

Department of Pathology, University of Geneva, CH 1211, Switzerland. 
Email: [email protected]

Infection of mice with Plasmodium Berghei Anka (PbA) leads to a thrombocytopenia, due to a reduced platelet life span, eventually associated with a syndrome of severe or cerebral malaria (CM). Thrombocytopenia was associated with an increase in the number of microparticles (mcp) in plasma. More than >60% of these mcp were of platelet origin, as seen by staining with an anti-platelet antibody. The thrombocytopenia and the amount of mcp were decreased in mice treated with anti CD40L mAb, suggesting that CD40L is the main effector of the thrombocytopenia. Caspase-1, -3, -6, -8, -9 were activated in platelets from infected mice, as seen by the binding of labeled probes or the amount of pro-caspase-3. Treatment of infected mice with the caspases inhibitor ZVAD-fmk decreased the number of mcp and the thrombocytopenia, shoving that platelet caspases are responsible for platelet fragmentation. In addition, the caspase inhibitor also caused a decrease in the mortality associated with CM, indicating a critical role of caspases in the expression of CM.

Immunogenetics 2001 Dec;53(9):736-740

Chromosomal mapping of the host resistance locus to rodent malaria ( Plasmodium yoelii) infection in mice.

Ohno T, Ishih A, Kohara Y, Yonekawa H, Terada M, Nishimura M.

Institute for Laboratory Animal Research, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan, 
Email: [email protected]

Abstract. The disease outcome in malaria caused by the protozoan parasite Plasmodium is influenced by host genetic factors. To identify host genes conferring resistance to infection with the malaria parasite, we undertook chromosomal mapping using a whole-genome scanning approach in cross-bred mice. NC/Jic mice all died with high parasitemia within 8 days of infection with 1×10(5) parasitized erythrocytes. In contrast, 129/SvJ mice all completely excluded malaria parasites from the circulation and remained alive 21 days after infection. We performed linkage analysis in backcross [(NC/Jicx129/SvJ)xNC/Jic] mice. The Pymr ( Plasmodium yoelii malaria resistance) locus was mapped to the telomeric portion of mouse Chromosome (Chr) 9. This locus controls host survival and parasitemia after infection. The Char1 locus ( P. chabaudi resistance locus 1), controlling host survival and peak parasitemia in P. chabaudi infection, was previously mapped to the same region. This host resistance locus mapping to Chr 9 may represent a ubiquitous locus controlling susceptibility to rodent malaria. Elucidation of the function of this gene will provide valuable insights into the mechanism of host defense against malaria parasite infection.

Immunogenetics 2002 Feb;53(10):894-899

Malaria is not responsible for the selection of TCR [beta]-subunit variable gene haplotypes in The Gambia.

Donaldson IJ, Shefta J, Hill AS, Boylston AW.

Molecular Medicine Unit, Clinical Sciences Building, St. James’s University Hospital, Leeds, LS9 7TF, UK.

Abstract. Previous work has shown that a single haplotype of the T-cell antigen receptor [beta]-subunit (TCRB) locus is predominant in African populations. This is likely to be due to selection pressure for gene(s) that protect children against disease. This study has tested the hypothesis that malaria is the responsible selection pressure, due to its impact on child mortality. The haplotypes of BV8S3, BV2S1, BV15S1, and BV3S1 were determined in children suffering from severe malaria and unaffected adult controls. No significant difference between cases and controls was shown for any of the haplotypes studied. In addition, an insertion/deletion (INDEL) haplotype in the 5[prime prime or minute] region of the TCRB locus was investigated. Again no differences between the two groups were detected. Therefore, the evidence suggests that malaria is not responsible for haplotype selection in The Gambia.

Immunogenetics 2002 Feb;53(10):884-893

Unique TCR [beta]-subunit variable gene haplotypes in Africans.

Donaldson IJ, Shefta J, Lawson CA, Bushnell JR, Morgan AW, Isaacs JD, Carpenter D, Shaw MA, Rooth I, Quinnell RJ, Zumla AM, Ollier WR, Chintu CZ, Muyinda GP, Hill AS, Boylston AW.

Molecular Medicine Unit, Level 6, Clinical Sciences Building, St. James’s University Hospital, Leeds, LS9 7TF, UK.

Abstract. This study investigated polymorphisms of genes in two regions of the T-cell antigen receptor [beta]-subunit (TCRB) locus, including BV9S2P, and BV6S7 in a 5[prime prime or minute] linkage group, and BV8S3, BV24S1, BV25S1, BV18S1, BV2S1, BV15S1 and BV3S1 in a 3[prime prime or minute] linkage group. These loci have been genotyped in individuals from five regions in Africa, including The Gambia, Nigeria, Cameroon, Tanzania, and Zambia, and in individuals from northern Britain, northern India, and Papua New Guinea (PNG). In the 3[prime prime or minute] linkage group, 11 unique haplotypes were identified in the combined African populations; two equally frequent haplotypes represent the majority of African chromosomes. One haplotype was found in all four regions studied. This is the most frequent haplotype in the northern British, northern Indian and PNG populations. Although present, it is infrequent in the African populations. A North-South gradient in the frequency of a common African haplotype was observed. The distribution did not represent that of a known disease. Evidence suggests that malaria is not responsible for selection of these haplotypes. Overall, this study highlights large differences in the genetic constitution of the TCRB locus between Africans and other populations.

QJM 2002 Feb;95(2):89-97

Plasma glutamine and glutamate concentrations in Gabonese children with Plasmodium falciparum infection.

Planche T, Dzeing A, Emmerson AC, Onanga M, Kremsner PG, Engel K, Kombila M, Ngou-Milama E, Krishna S.

Department of Infectious Diseases, St George’s Hospital Medical School, Cranmer Terrace, London, UK, Departement de Parasitologie, Mycologie et Medecine Tropicale and. Department de Biochimie, Faculte de Medecine et des Sciences de la Sante, Libreville, Gabon, Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon, Sektion Humanparasitologie, Institut fur Tropenmedizin, Universitaet Tubingen, Tubingen, Germany.

BACKGROUND: Low plasma glutamine levels in critical illness, neonates and burns patients are associated with poor outcome and increased risk of intercurrent infection. AIM: To investigate the relationship between plasma glutamine/glutamate levels and severity/outcome of malaria. DESIGN: Two-hospital prospective study, with both febrile and healthy controls. METHODS: We measured plasma glutamine and glutamate concentrations in 239 Gabonese patients: 145 children with malaria (86 with severe, 36 with moderate and 23 with uncomplicated disease), 42 healthy children, 44 febrile controls and eight healthy adults, and related findings to conventional markers of disease severity such as plasma lactate. RESULTS: Median (IQR) plasma glutamine was lower in uncomplicated falciparum malaria and in moderate malaria than in healthy controls: 353 (287–474) and 379 (293–448) vs. 485 (428–531) [micro]mol/l, respectively; p<0.01 for both malaria groups vs. controls. In contrast, plasma glutamine was within the normal range in those with severe malaria and in febrile control children: 431 (342–525) and 472 (338–547) [micro]mol/l, respectively. Furthermore, plasma glutamine was significantly higher in the children who died with malaria than in survivors: 514 (374–813) (n=12) vs. 399 (316–475) [micro]mol/l (n=133), respectively; p=0.001. There were no significant differences in plasma glutamate concentrations between any of the study groups. DISCUSSION: In severe malaria, there was a positive correlation between plasma glutamine and lactate levels (p=0.009, r=0.281). This correlation may reflect impaired gluconeogenesis. Glutamine supplementation is probably not justified in severe P. falciparum infection.

J Pharm Biomed Anal 2002 Apr 1;28(1):13-22

Preparation of [beta]-artemether liposomes, their HPLC–UV evaluation and relevance for clearing recrudescent parasitaemia in Plasmodium chabaudi malaria-infected mice.

Chimanuka B, Gabriels M, Detaevernier M, Plaizier-Vercammen JA.

Departement Farmaceutische Wetenschappen, Farmaceutische Technologie & Fysische Farmacie, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090, Brussels, Belgium

Egg phosphatidylcholine-cholesterol liposome formulations containing the antimalarial drug [beta]-artemether have been prepared and analyzed for their encapsulating capacity, chemical stability, leakage, in vitro release and their therapeutic efficiency against Plasmodium chabaudi infection. A HPLC–UV analysis of [beta]-artemether liposomes without derivatisation was achieved. A good linearity of y=4437.7x+469.01 (R(2)=0.9999) with a detection limit of 2 [mu]g ml([minus sign]1) was reached. Prior to this, liposomal formulations composed of different molar ratios of EPC-CHOL were prepared to select [beta]-artemether crystal-free liposome preparations. The formulation corresponding to 4:3 and a total concentration of 300 mg lipids ml([minus sign]1) buffer (pH 7.2), which could incorporate as much as 1.5 mg [beta]-artemether was selected for therapy. A trapping efficiency of nearly 100% was reached, the drug being located in the lipid bilayers. A dialysis test demonstrated that the drug could be reversibly released from the liposomes, reaching equilibrium within 24 h. After 3 months storage at 4 38–547) [micro]mol/l, respectively. Furthermore, plasma glutamine was significantly higher in the children who died with malaria than in survivors: 514 (374–813) (n=12) vs. 399 (316–475) [micro]mol/l (n=133), respectively; p=0.001. There were no signifiC, no leakage of [beta]-artemether had occurred indicating a high stability of the liposomes. These liposomes were used to treat mice infected with the virulent rodent malaria parasite Plasmodium chabaudi chabaudi, with a 100% cure by clearing the recrudescent parasitaemia.

J Immunol Methods 2002 Mar 1;261(1-2):73-83

Characterization of a unique human single-chain antibody isolated by phage-display selection on membrane-bound mosquito midgut antigens.

Foy BD, Killeen GF, Frohn RH, Impoinvil D, Williams A, Beier JC.

Interdisciplinary Program of Molecular and Cellular Biology, Tulane University, USA

The insect midgut is the primary site for food digestion, as well as for vector-borne pathogen infection into the invertebrate host. Accordingly, antigens of this critical insect organ are targets for anti-vector vaccines, insecticidal toxins, and transmission-blocking vaccines. We used midgut proteins of the African malaria vector mosquito Anopheles gambiae to select single-chain human antibody fragments (scFv) from a high-diversity, phage-displayed library. Using a phage-display selection method on western-blotted antigens, we selected an unusual truncated scFv clone, consisting of a heavy-chain only, which binds to An. gambiae midgut tissue. This clone binds a spectrum of mosquito antigens from the midgut and other mosquito tissues, as well as various mammalian glycoproteins, but binding was reduced when these glycoproteins were enzymatically deglycosylated. We also observed that this clone preferentially binds the lumenal midgut surface. Furthermore, antigen binding by our selected scFv was limited by competition with increasing concentrations of certain soluble carbohydrates, most dramatically by galactose and N-acetyl glucosamine. Our results show that the cognate epitope of this scFv is a carbohydrate moiety. This paper describes a phage-display selection of antibody fragments on mosquito midgut tissue and it also describes a method for phage-display selection on membrane-immobilized heterogeneous antigens. These selection methods resulted in the isolation of a novel, truncated, carbohydrate-binding human antibody fragment from a naive phage-display library.

Nature 2002 Feb 21;415(6874):905-9

Climate change and the resurgence of malaria in the East African highlands.

Hay SI, Cox J, Rogers DJ, Randolph SE, Stern DI, Shanks GD, Myers MF, Snow RW.

[1] TALA Research Group, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK [2] Kenya Medical Research Institute/Wellcome Trust Collaborative Programme, PO Box 43640, Nairobi, Kenya.

The public health and economic consequences of Plasmodium falciparum malaria are once again regarded as priorities for global development. There has been much speculation on whether anthropogenic climate change is exacerbating the malaria problem, especially in areas of high altitude where P. falciparum transmission is limited by low temperature. The International Panel on Climate Change has concluded that there is likely to be a net extension in the distribution of malaria and an increase in incidence within this range. We investigated long-term meteorological trends in four high-altitude sites in East Africa, where increases in malaria have been reported in the past two decades. Here we show that temperature, rainfall, vapour pressure and the number of months suitable for P. falciparum transmission have not changed significantly during the past century or during the period of reported malaria resurgence. A high degree of temporal and spatial variation in the climate of East Africa suggests further that claimed associations between local malaria resurgences and regional changes in climate are overly simplistic.

Rev Panam Salud Publica 2002 Jan;11(1):5-14

Relationships among immunity, nutrition, and malaria

[Article in Spanish]

Blair S, Carmona J, Correa A.

Grupo Malaria, Carrera 51 D No. 62-29, Laboratorio de Malaria, Facultad de Medicina, Universidad de Antioquia, Medellin, Colombia. 
Email: [email protected]

OBJECTIVE: To explore some relationships among immunity, nutrition, and malaria in a group of children from a population with a high endemic incidence of malaria. METHODS: This pilot descriptive prospective cross-sectional study was carried out in 1998 in the municipality of El Bagre, Antioquia, Colombia. Both boys and girls were studied in two groups: one group of 51 children had malaria and another group of 49 did not have malaria. The children with malaria had symptoms or signs of malaria and a positive thick blood film. The comparison group of 49 children without malaria (no signs or symptoms of malaria and a negative thick blood film) were chosen at random at government schools or children’s centers. For the study the following indices were calculated: weight-for-age, height-for-age, and weight-for-height. Also measured were the blood-serum concentrations of: albumin, prealbumin, apolipoprotein A1 (apoA1), transferrin, zinc, vitamin A, immunoglobulins G and M, interleukin-10 (IL-10), tumor necrosis factor-alpha, interferon-gamma, and lymphocyte populations. RESULTS: Of the children studied, 69% presented some risk of malnutrition, and 63% had some risk of chronic malnutrition. With regard to the immunity and biochemical variables, the children with malaria had less apoA1 and albumin and more IL-10 than did the children without malaria. All the biochemical variables showed lower averages in the group with malaria, risk of malnutrition, and immune or biochemical changes, while all the immunity variables had higher averages in that same group of children. CONCLUSIONS: 1) The high frequency of chronic malnutrition found clearly indicates the need for food supplementation measures. 2) The low values of prealbumin found could be due to the frequent bacterial or viral infections reported. 3) The serious vitamin A deficiency found calls for a supplementation program. 4) An association was found between low apoA1 values and the presence of malaria, but which one follows from the other is not known. 5) No relationship was observed between the anthropometric indicators of risk of malnutrition and the possible biochemical markers of malnutrition. 6) We found high levels of IL-10 in the children with malaria; this is the first time that this has been reported for Plasmodium vivax.

Eur J Immunol 2002 Mar;32(3):652-661

Cellular and molecular requirements for the recall of IL-4-producing memory CD4(+)CD45RO(+)CD27(–) T cells during protection induced by attenuated Plasmodium falciparum sporozoites.

Palmer D, Krzych U.

Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, USA.

The requirements for maintenance of antigen (Ag)-specific memory T cells in protection to malaria is poorly understood. We have previously demonstrated a recall of IL-4-producing memory CD4(+)CD45RO(+) T cells with parasitized red blood cells (pRBC) in persons protected by radiation-attenuated Plasmodium falciparum sporozoites ([gamma]-spz). Using the CD27 marker, we have now identified two subsets of CD4(+)CD45RO(+) T cells: CD4(+)CD45RO(+)CD27(+) T cells representing an early memory and CD4(+)CD45RO(+)CD27() T cells representing a terminally differentiated memory cells. A small subset of CD4(+)CD45RO(+)CD27(–) T cells also expressed CD70, the CD27 ligand. The addition of anti-CD70 monoclonal antibody (mAb) to pRBC-stimulated cultures significantly inhibited the conversion of CD27(+) to CD27(–) subset without profoundly affecting IL-4 production. In contrast, the inclusion of anti-CD27 mAb in parallel cultures abrogated IL-4 production without interfering with conscription of T cells into the CD27(–) T cell set. We propose that the persistence of memory CD4(+) T cells depends on Ag-driven conscription of a mature memory phenotype through co-ligation of CD27 and CD70 expressed, respectively, on CD27(+) and CD27(–) T cells. Hence, protracted protection in malaria depends in part on memory CD4(+) T cells that require specific Ag presumably from the repositories of liver-and blood-stage antigens and the delivery of a second signal from the CD27:CD70 interaction.

Infect Immun 2002 Mar;70(3):1581-90

Monoclonal antibody against the Plasmodium falciparum chitinase, PfCHT1, recognizes a malaria transmission-blocking epitope in Plasmodium gallinaceum ookinetes unrelated to the chitinase PgCHT1.

Langer RC, Li F, Popov V, Kurosky A, Vinetz JM.

World Health Organization Collaborating Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555, USA.

To initiate invasion of the mosquito midgut, Plasmodium ookinetes secrete chitinases that are necessary to cross the chitin-containing peritrophic matrix en route to invading the epithelial cell surface. To investigate chitinases as potential immunological targets of blocking malaria parasite transmission to mosquitoes, a monoclonal antibody (MAb) was identified that neutralized the enzymatic activity of the sole chitinase of Plasmodium falciparum, PfCHT1, identified to date. This MAb, designated 1C3, previously shown to react with an apical structure of P. falciparum ookinetes, also reacts with a discrete apical structure of P. gallinaceum ookinetes. In membrane feeding assays, MAb 1C3 markedly inhibited P. gallinaceum oocyst development in mosquito midguts. MAb 1C3 affinity isolated an approximately 210-kDa antigen which, under reducing conditions, became a 35-kDa antigen. This isolated 35-kDa protein cross-reacted with an antiserum raised against a synthetic peptide derived from the P. gallinaceum chitinase active site, PgCHT1, even though MAb 1C3 did not recognize native or recombinant PgCHT1 on Western blot. Therefore, this affinity-purified 35-kDa antigen appears similar to a previously identified protein, PgCHT2, a putative second chitinase of P. gallinaceum. Epitope mapping indicated MAb 1C3 recognized a region of PfCHT1 that diverges from a homologous amino acid sequence conserved within sequenced chitinases of P. berghei, P. yoelii, and P. gallinaceum (PgCHT1). A synthetic peptide derived from the mapped 1C3 epitope may be useful as a component of a subunit transmission-blocking vaccine.

Infect Immun 2002 Mar;70(3):1468-74

Naturally exposed populations differ in their T1 and T2 responses to the circumsporozoite protein of Plasmodium falciparum.

Reece WH, Plebanski M, Akinwunmi P, Gothard P, Flanagan KL, Lee EA, Cortina-Borja M, Hill AV, Pinder M.

Molecular Immunology Group, Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. 
Email: [email protected]

T-cell responses directed against the circumsporozoite protein (CS) of Plasmodium falciparum can mediate protection against malaria. We determined the frequency of T cells reactive to different regions of the CS in the blood of donors naturally exposed to P. falciparum by examining T1 (gamma interferon [IFN-gamma] ELISPOT assay), T2 (interleukin 4 [IL-4] ELISPOT assay), and proliferative T-cell responses. The proliferative responses were weak, which confirmed previous observations. The responses to the CS in the IL-4 and IFN-gamma ELISPOT assays were also weak (<40 responding cells per 10(6) cells), much weaker than the response to the purified protein derivative of Mycobacterium tuberculosis in the same donors. Moreover, a response in one assay could not be used to predict a response in either of the other assays, suggesting that although these assays may measure different responding cells, all of the responses are weakly induced by natural exposure. Interestingly, the two different study populations used had significantly different T1 and T2 biases in their responses in the C terminus of the protein, suggesting that the extent of P. falciparum exposure can affect regulation of the immune system.

Infect Immun 2002 Mar;70(3):1417-21

Induction of T helper type 1 and 2 responses to 19-kilodalton merozoite surface protein 1 in vaccinated healthy volunteers and adults naturally exposed to malaria.

Lee EA, Palmer DR, Flanagan KL, Reece WH, Odhiambo K, Marsh K, Pinder M, Gravenor MB, Keitel WA, Kester KE, Diggs C, Kaslow D, Apostolopoulos V, Ballou WR, Hill AV, Krzych U, Plebanski M.

Molecular Immunology Group, Nuffield Department of Medicine, Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom. 
Email: [email protected]

Plasmodium falciparum malaria is a major cause of death in the tropics. The 19-kDa subunit of P. falciparum merozoite surface protein 1 (MSP-1(19)), a major blood stage vaccine candidate, is the target of cellular and humoral immune responses in animals and humans. In this phase I trial of MSP-1(19), immunization of nonexposed human volunteers with either of the two allelic forms of recombinant MSP-1(19) induced high levels of antigen-specific Th1 (gamma interferon) and Th2 (interleukin 4 [IL-4] and IL-10) type lymphokines. The adjustment of the antigen dose and number of immunizations regulated the level of specificity of immune responses and Th1/Th2 bias of responses induced by vaccination. Novel conserved and allelic T-cell epitopes which induced cross-strain immune responses were identified. Importantly, responses to many of these novel epitopes were also present in adults exposed to malaria, both in east (Kenya) and west Africa (The Gambia). These data suggest that epitope-specific naturally acquired MSP-1(19) immune responses in endemic populations can be boosted by vaccination.

Trends Parasitol 2002 Mar;18(3):129-35

A multilateral effort to develop DNA vaccines against falciparum malaria.

Kumar S, Epstein JE, Richie TL, Nkrumah FK, Soisson L, Carucci DJ, Hoffman SL.

Malaria Program, Naval Medical Research Center, 20910, Silver Spring, MD, USA

Scientists from several organizations worldwide are working together to develop a multistage, multigene DNA-based vaccine against Plasmodium falciparum malaria. This collaborative vaccine development effort is named Multi-Stage DNA-based Malaria Vaccine Operation. An advisory board of international experts in vaccinology, malariology and field trials provides the scientific oversight to support the operation. This article discusses the rationale for the approach, underlying concepts and the pre-clinical development process, and provides a brief outline of the plans for the clinical testing of a multistage, multiantigen malaria vaccine based on DNA plasmid immunization technology.

Biochem Pharmacol 2002 Feb 1;63(3):393-8

Differential effects of 4-aminoquinoline-containing antimalarial drugs on hemoglobin digestion in Plasmodium falciparum-infected erythrocytes.

Famin O, Ginsburg H.

Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel

Several reports suggest that the antimalarial mode of action of quinoline drugs may differ in their mechanistic details. The malaria parasite Plasmodium falciparum was treated in culture with chloroquine, amodiaquine, quinine and mefloquine in a dose- and time-dependent fashion. After removal of the drug, the viability of the parasites and their hemoglobin content were determined. Whereas in the presence of chloroquine and amodiaquine, there was a correlation between parasite killing and accumulation of hemoglobin, with quinine and mefloquine parasite killing was not associated with the accumulation of hemoglobin. Mefloquine inhibited the chloroquine-dependent accumulation of hemoglobin. It is suggested that whereas chloroquine and amodiaquine inhibit the digestion of hemoglobin, mefloquine and possibly quinine inhibit the ingestion of host cell hemoglobin by interfering with the ingestion process. These results may explain the demonstrable antagonism between chloroquine and mefloquine and their antipodal sensitivity to these drugs.

Trop Med Int Health 2002 Jan;7(1):45-52

Use of clinical algorithms for diagnosing malaria.

Chandramohan D, Jaffar S, Greenwood B.

Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.

Several attempts have been made to identify symptoms and signs based algorithms for diagnosing malaria. In this paper, we review the results of published studies and assess the risks and benefits of this approach in different epidemiological settings. Although in areas with a low prevalence the risk of failure to treat malaria resulting from the use of algorithms was low, the reduction in the wastage of drugs was trivial. The odds of wastage of drugs increased by 1.49 (95% confidence limit 1.45-1.51) for each 10% decrease in the prevalence of malaria. In highly endemic areas the algorithms had a high risk of failure to treat malaria. The odds of failure to treat increased by 1.57 (95% confidence limit 1.50-1.65) for each 10% increase in the prevalence. Furthermore, the best clinical algorithms for diagnosing malaria were site-specific. We conclude that the accuracy of clinical algorithms for diagnosing malaria is not sufficient to determine whether antimalarial drugs should be given to children presenting with febrile illness. In highly endemic areas where laboratory support is not available, the policy of offering antimalarial drugs to all children presenting with a febrile illness recommended by the integrated child management initiative is appropriate.

Trop Med Int Health 2002 Jan;7(1):29-34

Weekly chloroquine prophylaxis and the effect on maternal haemoglobin status at delivery.

Salihu HM, Naik EG, Tchuinguem G, Bosny JP, Dagne G.

Department of Obstetrics and Gynecology, Ebolowa Regional Hospital, Cameroon, Department of Biostatistics and Epidemiology, College of Public Health, University of South Florida, Tampa, FL, USA.

Our aim was to determine the effectiveness of chloroquine prophylaxis in reducing the frequency of malaria-induced anaemia at delivery. We estimated the haemoglobin levels of 207 parturients; 82 (39.6%) had been on chloroquine prophylaxis [treatment group (TG)] while 125 (60.4%) did not take any malaria preventive medication antenatally [control group (CG)]. The proportion of women with malaria parasitaemia was significantly higher in CG than TG [risk ratio (RR=1.57, CI=1.05-2.34)]. The dose-response relationship between the severity of parasitaemia and the risk of being anaemic (P < 0.001) confirms a strong correlation between gestational malaria and maternal anaemia. There was a 35% reduction in risk for anaemia in the TG compared with the CG (RR=0.65, 0.40-1.06). The difference in risk was more pronounced after adjusting for disparity in place of residence, educational status and obstetric history (adjusted RR=0.54, CI=0.21-0.98). Primiparous mothers appeared to have benefited more from the antianaemic effects of malaria chemoprevention than mothers of higher parity (protective effectiveness 43% compared with 33%, respectively). In conclusion, despite reports of widespread Plasmodium falciparum resistance to chloroquine on the African continent, malaria chemosuppression with the drug was found beneficial in reducing the risk of anaemia at delivery among Cameroonian women.

Trop Med Int Health 2002 Jan;7(1):19-28

Malaria in pregnancy in rural Mozambique: the role of parity, submicroscopic and multiple Plasmodium falciparum infections.

Saute F, Menendez C, Mayor A, Aponte J, Gomez-Olive X, Dgedge M, Alonso P.

Centro de Investigacao em Saude da Manhica, Instituto Nacional de Saude, Maputo, Mozambique.

BACKGROUND: Falciparum malaria affects pregnant women, especially primigravidae, but before malaria control programmes targeted to them can be designed, a description of the frequency and parity pattern of the infection is needed. There is little information on the frequency and effect of submicroscopic malaria infection, as well as on multiplicity of Plasmodium falciparum genotypes in pregnancy. This study aimed to describe the prevalence of malaria parasitaemia and anaemia and their relation to parity and age in pregnant women, during two malaria transmission seasons in a rural area of southern Mozambique. It also tried to assess the frequency and effect on anaemia of submicroscopic and multiple falciparum infections. METHODS: A total of 686 pregnant women were enrolled in three cross-sectional community-based surveys during different transmission seasons in rural southern Mozambique. In each survey a questionnaire was administered on previous parity history, the gestational age was assessed, the axillary temperature recorded and both haematocrit and malaria parasitaemia were determined. We used polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis to determine submicroscopic and multiple P. falciparum infections in a subsample of women. FINDINGS: A total of 156 women (23%) had microscopic parasitaemia, of which 144 (92%) were asexual forms of P. falciparum. The prevalence of clinical malaria was 18 of 534 (3%), that of anaemia, 382 of 649 (59%). In a multivariate analysis age but not parity was associated with an increased risk of microscopic parasitaemia. Anaemia was associated with microscopic P. falciparum parasitaemia. Both malaria parasitaemia and anaemia were more frequent during the rainy season. Although not statistically significant, submicroscopic infections tended to be more frequent among grand-multiparous pregnant women. Subpatent infections were not associated with increased anaemia. Multiplicity of infection was not associated with either parity, age or anaemia. Likewise, there was no correlation between P. falciparum density and multiplicity of infection. INTERPRETATION: We did not observe a clear parity pattern of malaria and anaemia in our study. It is possible although unlikely that selection bias may have influenced these findings; but in which direction is unclear. The importance of locally based research before implementation of public health measures needs to be highlighted. According to our findings, a more cost-effective malaria control approach in this area would be targeting all pregnant women regardless of their parity. This would be also more feasible logistically as it would not rely on accurate ascertainment of parity, something that is not always easy in busy antenatal clinics.

Antimicrob Agents Chemother 2002 Mar;46(3):778-782

Oral Artesunate Dose-Response Relationship in Acute Falciparum Malaria.

Angus BJ, Thaiaporn I, Chanthapadith K, Suputtamongkol Y, White NJ.

Faculty of Tropical Medicine, Mahidol University, Bangkok 10400. Sangklaburi Hospital, Sangklaburi, Kanchanaburi Province, Thailand. Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom.

The combination of an oral artemisinin derivative (usually artesunate) and mefloquine has become standard treatment for multidrug-resistant falciparum malaria in several parts of Southeast Asia. The doses of artesunate used in monotherapy and combination treatment have largely been derived empirically. In order to characterize the in vivo dose-response relationship for artesunate and thus rationalize dosing, 47 adult patients with acute uncomplicated falciparum malaria and parasitemia [greater-than-or-equal]1% were randomized to receive a single oral dose of artesunate varying between 0 and 250 mg together with a curative dose of oral mefloquine. Acceleration of parasite clearance was used as the pharmacodynamic variable. An inhibitory sigmoidal maximum effect (E(max)) pharmacodynamic model typical of a dose-response curve was fitted to the relationship between dose and shortening of parasite clearance time (PCT). The E(max) was estimated as 28.6 oral h, and the 50% effective concentration was 1.6 mg/kg of body weight. These results imply that there is no reduction in PCTs with the use of single doses of artesunate higher than 2 mg/kg, and this therefore reflects the average lower limit of the maximally effective dose.

Trends Parasitol 2002 Jan;18(1):39-45

DNA microarrays for malaria.

Rathod PK, Ganesan K, Hayward RE, Bozdech Z, DeRisi JL.

Dept of Chemistry, University of Washington, 98195, Seattle, WA, USA

DNA microarrays are a powerful tool for the analysis of RNA and DNA composition on a whole-genome scale. The first applications of this technology in parasitology are in place. This review examines the various approaches to Plasmodium transcript-profiling that are being adopted using DNA microarray analysis and discusses additional strategies for obtaining and collating information relevant to the search for drug and vaccine candidates in malaria.

Trends Parasitol 2002 Jan;18(1):32-8

Plasmodium sex determination and transmission to mosquitoes.

Paul RE, Brey PT, Robert V.

Unite de Biochimie et Biologie Moleculaire des Insectes, Institut Pasteur, 28 rue du Dr Roux, 75724 Cedex 15, Paris, France. 
Email: [email protected]

In order to be transmitted by their mosquito vector, malaria parasites undergo sexual reproduction, which occurs between specialized male and female parasites (gametes) within the blood meal in the mosquito. Nothing was known about how Plasmodium determines the sex of its gametocytes (gamete precursors), which are produced in the vertebrate host. Recently, erythropoietin, the vertebrate hormone controlling erythropoiesis in response to anaemia, was implicated in Plasmodium sex determination in animal models of malaria. This review examines the available information and addresses the relevance of such a sex determining mechanism for Plasmodium falciparum transmission to mosquitoes, with special reference to low gametocytaemias.

Trends Parasitol 2002 Jan;18(1):12-6

The cost of not treating bednets.

Guyatt HL, Snow RW.

Kenya Medical Research Institute/Wellcome Trust Collaborative Programme, PO Box 43640, Kenyatta National Hospital, Nairobi, Kenya

For centuries, bednets have been used as a physical barrier against biting insects. Recent epidemiological investigations into their protective effects against malaria were quickly overtaken by studies focusing on the benefits of impregnating bednets with insecticide. The operational problems encountered in re-treating bednets with insecticide are often cited as an impediment to wide-scale implementation. The evidence for a protective effect of untreated nets against malaria is presented here alongside an analysis of how well untreated nets would need to work in order to compete with treated nets within a cost-effectiveness framework.

Mol Biochem Parasitol 2002 Mar;120(1):41-52

Merozoite surface protein-9 of Plasmodium vivax and related simian malaria parasites is orthologous to p101/ABRA of P. falciparum.

Vargas-Serrato E, Barnwell JW, Ingravallo P, Perler FB, Galinski MR.

Department of Medicine, Emory Vaccine Research Center, Yerkes Primate Research Center, Emory University, 954 Gatewood Rd., 30329, Atlanta, GA, USA

Plasmodium vivax merozoite surface protein-9 (Pvmsp-9) is characterized here along with orthologues from the related simian malarias Plasmodium cynomolgi and Plasmodium knowlesi. We show that although the corresponding MSP-9 proteins do not have acidic-basic repeated amino acid (aa) motifs, they are related to the Plasmodium falciparum acidic-basic repeat antigen (ABRA) also known as p101. Recognition of this new interspecies Plasmodium MSP family stems from the prior identification of related MSP termed PvMSP-185, PcyMSP-150, and PkMSP-110 on the surface of P. vivax, P. cynomolgi and P. knowlesi merozoites. A clone containing the nearly complete P. knowlesi gene encoding PkMSP-110/MSP-9 provided a hybridization probe and initial sequence information for the design of primers to obtain the P. vivax and P. cynomolgi orthologues using polymerase chain reaction (PCR) amplification strategies. The P. vivax, P. cynomolgi and P. knowlesi msp-9 genes encode proteins that range in calculated molecular mass from 80 to 107 kDa, have typical eukaryotic signal peptides and diverse repeated motifs present immediately upstream of their termination codon. Another feature conserved among these proteins, including the P. falciparum ABRA protein, is the positions of four cysteine residues near the N-terminus, suggesting this conservation maintains structural and perhaps functional characteristics in the MSP-9 family. Rabbit polyclonal antisera raised against recombinantly expressed N-termini of P. knowlesi and P. vivax MSP-9 cross-react with the counterpart proteins in immunofluorescence and immunoblot assays. Comparative interspecies investigations of the potential role(s) of Plasmodium MSP-9 in merozoite invasion of erythrocytes and as a malaria vaccine candidate can now be pursued.

Br J Clin Pharmacol 2002 Jan;53(1):49-57

Pharmacokinetics and anticonvulsant effects of diazepam in children with severe falciparum malaria and convulsions.

Ogutu BR, Newton CR, Crawley J, Muchohi SN, Otieno GO, Edwards G, Marsh K, Kokwaro GO.

Kenya Medical Research Institute [KEMRI]/Wellcome Trust Centre for Geographic Medicine Research (Coast), Kilifi, Department of Pharmaceutics and Pharmacy Practice, Faculty of Pharmacy, University of Nairobi, Nairobi, Centre for Clinical Research-KEMRI, Nairobi, Kenya, Neurosciences Unit, Institute of Child Health, University of London, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool and Division of Parasite and Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK.

AIMS: Convulsions are a common complication of severe malaria in children and are associated with poor outcome. Diazepam is used to terminate convulsions but its pharmacokinetics and pharmacodynamics have not been studied in this group. Accordingly, we carried out a comparative study of the pharmacokinetics of intravenous (i.v.) and rectal (p.r.) diazepam. METHODS: Twenty-five children with severe malaria and a convulsion lasting >5 min were studied. Sixteen children received diazepam intravenously (i.v.; 0.3 mg kg[minus sign]1) and nine rectally (p.r.; 0.5 mg kg[minus sign]1). Plasma diazepam concentrations were measured by reversed phase high-performance liquid chromatography. The duration of convulsions, depth of coma, respiratory and cardiovascular parameters were monitored. RESULTS: Median maximum plasma diazepam concentrations of 634 (range 402–1507) ng ml[minus sign]1 and 423 (range 112–1953) ng ml[minus sign]1 were achieved at 5 and 25 min following i.v. and p.r. administration, respectively. All patients except three (one i.v. and two p.r.) achieved plasma diazepam concentration >200 ng ml[minus sign]1 within 5 min. Following p.r. administration, plasma diazepam concentrations were more variable than i.v. administration. A single dose of i.v. diazepam terminated convulsions in all children but in only 6/9 after p.r. administration. However, nine children treated with i.v. and all those treated with p.r. diazepam had a recurrence of convulsions occurring at median plasma diazepam concentrations of 157 (range: 67–169) and 172 (range: 74–393) ng ml[minus sign]1, respectively. All the children in the i.v. and four in the PR diazepam group who had recurrence of convulsions required treatment. None of the children developed respiratory depression or hypotension. CONCLUSIONS: Administration of diazepam i.v. or p.r. resulted in achievement of therapeutic concentrations of diazepam rapidly, without significant cardio-respiratory adverse effects. However, following p.r. administration, diazepam did not terminate all convulsions and plasma drug concentrations were more variable.

Br J Clin Pharmacol 2002 Jan;53(1):23-30

The pharmacokinetic properties of intramuscular artesunate and rectal dihydroartemisinin in uncomplicated falciparum malaria.

Ilett KF, Batty KT, Powell SM, Binh TQ, Thu LT, Phuong HL, Hung NC, Davis TM.

Department of Pharmacology, University of Western Australia, Nedlands, Clinical Pharmacology and Toxicology Laboratory, Western Australian Centre for Pathology and Medical Research, Nedlands, Department of Medicine, University of Western Australia, Fremantle Hospital, Fremantle, School of Pharmacy, Curtin University of Technology, Bentley, Australia, Tropical Diseases Research Center, Cho Ray Hospital, Ho Chi Minh City and Bao Loc Hospital, Lam Dong Province, Vietnam.

AIMS: To obtain pharmacokinetic data for artesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) following i.m. ARTS and rectal DHA administration. METHODS: Twelve Vietnamese patients with uncomplicated falciparum malaria were randomized to receive either i.v. or i.m. ARTS (120 mg), with the alternative preparation given 8 h later in an open crossover design. A further 12 patients were given i.v. ARTS (120 mg) at 0 h and rectal DHA (160 mg) 8 h later. RESULTS: Following i.v. bolus, ARTS had a peak concentration of 42 [micro]m (16 mg l[minus sign]1), elimination t1/2 = 3.2 min, CL = 2.8 l h[minus sign]1 kg[minus sign]1 and V = 0.22 l kg[minus sign]1. The Cmax for DHA was 9.7 [micro]m (2.7 mg l[minus sign]1), t1/2 = 59 min, CL = 0.64 l h[minus sign]1 kg[minus sign]1 and V = 0.8 l kg[minus sign]1. Following i.m. ARTS, Cmax was 2.3 [micro]m (3.7 mg l[minus sign]1), the apparent t1/2 = 41 min, CL = 2.9 l h[minus sign]1 kg[minus sign]1 and V = 2.6 l kg[minus sign]1. The relative bioavailability of DHA was 88%, Cmax was 4.1 [micro]m (1.16 mg l[minus sign]1) and t1/2 = 64 min. In the rectal DHA study, relative bioavailability of DHA was 16%. CONCLUSIONS: For patients with uncomplicated falciparum malaria i.m. ARTS is a suitable alternative to i.v. ARTS, at equal doses. To achieve plasma DHA concentrations equivalent to parenteral administration of ARTS, rectal DHA should be given at approximately four-fold higher milligram doses. Further studies are needed to determine whether these recommendations can be applied to patients with severe malaria.

S Afr Med J 2001 Nov;91(11):975-8

Therapeutic efficacy of sulfadoxine-pyrimethamine in uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga.

Mabuza A, Govere J, Durrheim D, Mngomezulu N, Bredenkamp B, Barnes K, Sharp B.

Mpumalanga Department of Health, Nelspruit, Mpumalanga.

OBJECTIVES: To assess therapeutic efficacy of sulfadoxine-pyrimethamine (SP) in treatment of uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga, South Africa. SETTING: Tonga district with a population of 116,418 and subject to seasonal malaria, with an average annual incidence of 3,200 cases. SUBJECTS: One hundred and nineteen malaria patients presenting to a sentinel surveillance clinic and recruited according to World Health Organisation (WHO) criteria. METHODOLOGY: Patients satisfying WHO inclusion criteria were treated with a single oral dose of SP and the response of infection to treatment in each patient was routinely monitored clinically and parasitologically on days 1, 2, 3, 7, 14, 21, 28 and 42 post-treatment. One hundred and ten patients completed follow-up to day 42 or evidence of clinical or parasitological failure. RESULTS: The cure rate at day 42 was 93.6% (103/110). Two patients (1.8%, RII) were early treatment failures on day 3, while recrudescence (4.5%, RI) occurred in 5 patients on day 28 (N = 3) and on day 42 (N = 2). CONCLUSION: In Mpumalanga P. falciparum remains sensitive to SP, with no significant difference between the baseline cure rate (94.5%) and the cure rate in the present study (93.6%).

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