Library Malaria Bulletin No. 31: Feb 19-28,
Soc Sci Med 2002
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
S Afr Med J 2001
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
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
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]
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
Surface Protein 3 and Protection against Malaria in Aotus
Hisaeda H, Saul A, Reece JJ, Kennedy MC, Long CA, Miller LH,
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
J Infect Dis 2002 Mar 1;185(5):650-6
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]
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
Apoptosis 2002 Apr;7(2):91-8
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,
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
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
Email: [email protected]
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 1x10(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
[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
QJM 2002 Feb;95(2):89-97
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.
J Pharm Biomed Anal
2002 Apr 1;28(1):13-22
[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
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
of a unique human single-chain antibody isolated by
phage-display selection on membrane-bound mosquito midgut
Foy BD, Killeen GF, Frohn RH, Impoinvil D, Williams A, Beier
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
Nature 2002 Feb 21;415(6874):905-9
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.
 TALA Research Group, Department of Zoology, University of
Oxford, South Parks Road, Oxford OX1 3PS, UK  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
among immunity, nutrition, and malaria
Blair S, Carmona J, Correa A.
Grupo Malaria, Carrera 51 D No. 62-29, Laboratorio de Malaria,
Facultad de Medicina, Universidad de Antioquia, Medellin,
Email: [email protected]atios.udea.edu.co
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
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
Infect Immun 2002 Mar;70(3):1581-90
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
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]
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]
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.
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
2002 Feb 1;63(3):393-8
effects of 4-aminoquinoline-containing antimalarial drugs on
hemoglobin digestion in Plasmodium falciparum-infected
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
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
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,
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
Trop Med Int Health 2002 Jan;7(1):19-28
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
Artesunate Dose-Response Relationship in Acute Falciparum
Angus BJ, Thaiaporn I, Chanthapadith K, Suputtamongkol Y,
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
Trends Parasitol 2002 Jan;18(1):39-45
microarrays for malaria.
Rathod PK, Ganesan K, Hayward RE, Bozdech Z, DeRisi JL.
Dept of Chemistry, University of Washington, 98195, Seattle, WA,
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
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,
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,
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
Mol Biochem Parasitol 2002 Mar;120(1):41-52
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,
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
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
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
efficacy of sulfadoxine-pyrimethamine in uncomplicated
Plasmodium falciparum malaria 3 years after introduction in
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%).