EHP Library Malaria Bulletin 48: Oct 28-Nov 10, 2002

 
                           Social Sciences and Malaria
 
Soc Sci Med  2002 Dec;55(11):2061-72 
 
Afghan refugees and the temporal and spatial distribution of malaria in
Pakistan.
 
Rowland M, Rab MA, Freeman T, Durrani N, Rehman N.
 
HealthNet International, University Town, Peshawar, Pakistan
 
Influx of refugees and establishment of camps or settlements in malaria endemic
areas can affect the distribution and burden of malaria in the host country.
Within a decade of the Soviet invasion of Afghanistan and the arrival of 2.3
million Afghan refugees in Pakistan's North West Frontier Province, the annual
burden of malaria among refugees had risen ten fold from 11,200 cases in 1981 to
118,000 cases in 1991, a burden greater than the one reported by the Pakistan
Ministry of Health for the entire Pakistani population. Political developments
in the 1990s led to over half the refugee population repatriating to
Afghanistan, and the Afghan Refugee Health Programme (ARHP) was scaled down
proportionately. Districts in which the ARHP recorded a reduced incidence of
malaria began to show an increased incidence in the statistics of the Pakistan
government health programme. This and other evidence pointed to a change in
health seeking practices of the refugees who remained in Pakistan, with many
turning from ARHP to Pakistani health services as aid declined. Comparison of
the two sources of data produced no evidence for the spatial distribution of
malaria in NWFP having changed during the 1990s. Nor was there any evidence for
the presence of refugees having increased the malaria burden in the Pakistani
population, as is sometimes alleged. This highlights the risk of misinterpreting
health trends when parallel health services are operating. Over the decade
incidence in the refugee camps decreased by 25% as a result of control
activities, and by 1997 the burden among remaining refugees had fallen to 26,856
cases per annum. These trends indicate that the burden would continue to fall if
political conditions in Afghanistan were to improve and more refugees returned
to their homeland.
 
Soc Sci Med  2002 Dec;55(12):2215-26 
 
Strategies to improve adherence to recommended chloroquine treatment regimes:
a quasi-experiment in the context of integrated primary health care delivery
in Ghana.
 
Agyepong IA, Ansah E, Gyapong M, Adjei S, Barnish G, Evans D.
 
District Health Administration, P.O. Box 1, Dodowa, Ghana
 
This paper presents the results of an intervention study carried out as part of
the activities of a District Health Management Team responsible for integrated
primary health care delivery in a rural district in Ghana. The aim was to test
the impact of a combination of improved information provision to patients and
drug labeling on adherence to recommended anti-malarial treatment regimens
focusing on oral chloroquine, for the outpatient management of acute
uncomplicated malaria. The study had a quasi-experimental pre-test post-test
control group design with partly random allocation by clinic. The results show
that the intervention resulted in an improved flow of information to clients
prescribed chloroquine, and better labeling of drugs for the home treatment of
acute clinical episodes of malaria in the intervention area. Improvements in
adherence occurred in all clinics. However, improvements in adherence were most
marked in the clinic that was worst performing at the start of the intervention.
Implications of the results for improving adherence to chloroquine therapy on an
outpatient basis are discussed.
 
Health Policy Plan  2002 Dec;17(4):402-411 
 
Willingness to pay for treated mosquito nets in Surat, India: the design and
descriptive analysis of a household survey.
 
Bhatia M, Fox-Rushby J.
 
Department of Social Policy, London School of Economics and Political Science,
and. Department of Public Health and Policy, London School of Hygiene and
Tropical Medicine, London, UK.
 
For willingness to pay (WTP) studies to have an appropriate impact on policy
making, it is essential that the design and analysis are undertaken carefully.
This paper aims to describe and justify the design of the survey tool used to
assess hypothetical WTP for treated mosquito nets (TMN) in rural Surat, India
and report its findings. Results from qualitative work were used as an input for
developing the WTP questionnaire. A total of 1200 households belonging to 80
villages in rural Surat were selected for the study. A bidding format was used
to elicit WTP values, using three different starting bids. The scenario was
constructed in a way to reduce the possibility of respondents acting
strategically. The response rate was 100%. About 79% of the respondents were
willing to buy TMNs and the mean WTP was Rs57. Descriptive results of economic
and other taste and preference variables are also presented, which include
preventive measures used by households and treatment seeking behaviour for
malaria. It is observed that WTP as well as demographic variables and prevention
methods differ significantly across arms of the trial. This paper suggests that
policy-makers could use the evidence following further analysis, along with
information on costs of implementation, to ascertain the levels of subsidy that
may be needed at different levels of coverage.
 
Health Policy Plan  2002 Dec;17(4):333-344 
 
Self-treatment for malaria: the evidence and methodological issues.
 
McCombie S.
 
Department of Anthropology and Geography, Georgia State University, Atlanta, GA,
USA.
 
Malaria remains an important cause of death, especially in sub-Saharan Africa.
Self-treatment with antimalarial drugs is a common practice that raises
important issues for policy-makers. A number of important questions concerning
factors related to self-treatment, adequacy of self-treatment and the role of
self-treatment in malaria mortality remain unanswered. Although there are some
common patterns, there is considerable diversity in treatment practices, even
within a single country. Social science research on malaria treatment needs to
move beyond description to evaluation of interventions. This will require a
greater degree of methodological rigour and more attention to the generation of
data that can be compared across time periods and studies. Definitions of
malaria cases and the role of local disease categories in identifying cases need
to be made more explicit. Illnesses should be classified by severity, using
measures of perceived severity as well as biomedical signs of severity. Each
treatment step should be considered in terms of four levels of analysis: who
provided the treatment or advice, what the treatment was, where it was obtained
and when it was taken in relationship to onset of illness.
 
Public Health  2002 Nov;116(6):374-8 
 
Improvement in malaria services in an urban setting: role of staff motivation.
 
Raghuvanshi VS.
 
Urban health centres and the private clinics (PCs) providing malaria services in
an urban setting were compared on seven utilization-determining factors to
assess why people preferred one over the other. On the other hand, motivation
level of the technical staff of the corporation in the malaria services was
studied to find out the extent to which the motivation level of the staff was
responsible for the observed mean scores of the factors studied. It was found
that PCs fared better on all of them. However, the two differed mostly on
wait-in period at the outlet, distance from residence, ambience of the outlet,
and getting relief. The study further showed that for the doctors and the
primary health workers, the opportunity of influencing people was the strongest
motivation to work in the corporation and for the subsanitary inspectors, it was
affiliation. Based on this, a model is suggested to introduce changes based on
motivation mix of the malaria staff.
 
Trop Doct  2002 Oct;32(4):206-9 
 
Treatment of malaria in Ethiopian folk medicine.
 
Gedif T, Hahn HJ.
 
Institute of Pharmacoepidemiology and Pharmacoeconomics, School of Pharmacy,
Martin-Luther University, Halle(Saale), Germany. Email: [email protected]
 
Key informant interviews of herbalists were conducted to document the
traditional management of malaria in Ethiopia. The perceptions of the cause and
symptoms of malaria, the use of plants, their preparation and administration
were recorded. Interviews were performed in rural Butajira and Addis Ababa (the
main city). The result showed that 33 (75%) of the interviewed healers treat
malaria using herbal drugs. Sixteen plants were reported to have been used of
which eight were used as a single remedy and the rest as composite remedies with
other plants. The ethnopharmacological data generated in this study on
antimalarial plants is useful for further evaluations of the traditional claims
of antimalarial plants in Ethiopia.
 
                                       PubMed
 
Genes Immun  2002 Nov;3(7):414-418 
 
A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) 
is associated with mortality from cerebral malaria and with reduced nitric
oxide production.
 
Morahan G, Boutlis CS, Huang D, Pain A, Saunders JR, Hobbs MR, Granger DL,
Weinberg JB, Peshu N, Mwaikambo ED, Marsh K, Roberts DJ, Anstey NM.
 
The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC,
Australia.
 
Interleukin-12 (IL-12) is an important regulatory cytokine in infection and
immunity. Administration of IL-12 may reduce complications of severe malaria in
rodents. Polymorphisms in IL12B, the gene encoding the IL-12 p40 subunit,
influence the secretion of IL-12 and susceptibility to Type 1 diabetes. We
therefore investigated whether IL12B polymorphisms may affect the outcome of
severe malaria. Homozygosity for a polymorphism in the IL12B promoter was
associated with increased mortality in Tanzanian children having cerebral
malaria but not in Kenyan children with severe malaria. Furthermore, homozygotes
for the IL12B promotor polymorphism had decreased production of nitric oxide,
which is in part regulated by IL-12 activity. These studies suggest that IL12B
polymorphisms, via regulation of IL-12 production, may influence the outcome of
malaria infection in at least one African population.
doi:10.1038/sj.gene.6363909
 
J Membr Biol  2002 Nov;190(1):1-8 
 
A novel transporter, pfcrt, confers antimalarial drug resistance.
 
Howard EM, Zhang H, Roepe PD.
 
Dept. of Chemistry, Dept. of Biochemistry and Molecular Biology, and Program in
Tumor Biology, Lombardi Cancer Center Georgetown University, 37th and O Streets,
Washington, DC 20057-1227, USA.
 
The elucidation of the molecular details of drug resistance phenomena is a very
active area of research that crosses many disciplinary boundaries. Drug
resistance is due to altered drug-target interaction, and/or dysregulated
signaling related to cell growth and death. Since many drugs need to rapidly
diffuse into and within cells in order to find their targets, and since
transmembrane ion transport is an important facet of cellular signaling, it is
not surprising that membrane transport phenomena have been implicated in the
evolution of drug resistance in tumor cells, bacteria, and intracellular
parasites such as Plasmodium falciparum, the causative agent of the most lethal
form of human malaria. The most infamous membrane transport protein involved in
drug resistance is "MDR protein" or "P-glycoprotein" (Pgp),1 which was found to
be overexpressed in drug-resistant tumor cells over 15 years ago, and which is
representative of the ATP-binding cassette (ABC) superfamily that also includes
the important cystic fibrosis transmembrane conductance regulator (CFTR) and
sulfonyl urea receptor (SUR) ion channels. Availability of mouse and human Pgp
cDNA rather quickly led to the identification of homologues in many species,
including P. falciparum, and these were de facto assumed to be the ultimate
determinants of drug resistance in these systems as well. However, research over
the past 10 years has taught us that this assumption likely is wrong and that
the situation is more complex. We now know that human Pgp plays a relatively
minor role in clinically relevant tumor drug resistance, and that an integral
membrane protein with no homology to the ABC superfamily, Pfcrt, ultimately
confers chloroquine resistance in P. falciparum. Thus, the general hypothesis
that membrane transport and membrane transport proteins are important in drug
resistance phenomena remains correct, but at a genetic, biochemical, and
physiological level we have recently witnessed a few very interesting surprises.
 
Trends Mol Med  2002 Nov;8(11):531-7 
 
Human complement receptor type 1 (CR1) binds to a major malarial adhesin.
 
Krych-Goldberg M, Moulds JM, Atkinson JP.
 
Division of Rheumatology, Washington University School of Medicine, 63110, St.
Louis, MO, USA
 
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a major adhesin
molecule expressed on Plasmodium-falciparum-infected erythrocytes, interacts
with several receptors on endothelial cells and uninfected erythrocytes. This
'stickiness', known as rosetting, is a strategy used by the parasite to remain
sequestered in the microvasculature to avoid destruction in the spleen and
liver. Erythrocyte rosetting causes obstruction of the blood flow in
microcapillaries. Recent data suggest a direct interaction between PfEMP1 and a
functional site of complement receptor type 1 (CR1; CD35) on uninfected
erythrocytes. Consistent with the hypothesis that CR1 is important in malaria
pathogenesis is a 40-70-fold increase in the frequency of two CR1 blood-group
antigens (at least one of which might rosette less efficiently) in
malaria-exposed African populations. Furthermore, structural differences in
erythrocyte CR1 between human and non-human primates are probably explained by
the selective pressure of malaria.
 
Parasitol Int  2002 Dec;51(4):343-52 
 
Differential localization of processed fragments of Plasmodium falciparum 
serine repeat antigen and further processing of its N-terminal 47 kDa fragment.
 
Li J, Mitamura T, Fox BA, Bzik DJ, Horii T.
 
Department of Molecular Protozoology, Research Institute for Microbial Diseases,
Osaka University, Suita, 565-0871, Osaka, Japan
 
The serine repeat antigen (SERA) of Plasmodium falciparum is a blood stage
malaria vaccine candidate. It has been shown that 120 kDa SERA was
proteolytically processed into N-terminal 47 kDa fragment (P47), central 56 kDa
fragment (P56) that was further converted to 50 kDa (P50), and C-terminal 18 kDa
fragment (P18). Here, we have examined the processing of SERA and the
localization of its processed fragments by using mouse antibodies directed
against recombinant proteins corresponding to different domains of SERA. Western
blot analysis showed that all the processing events occurred inside parasitized
erythrocytes at the stage just prior to the schizont rupture, that P47 was
further processed into two 25 kDa fragments and that the two fragments, which
were linked to P18 through disulfide bonds, were associated with the merozoite.
In contrast, P50 was completely shed into culture medium and absent from the
merozoite. This observation was further supported by the results of indirect
immunofluorescence assay. These results could account for the findings that
antibodies against P47 were inhibitory to the parasite growth in vitro but those
against P50 were not. Finally, we demonstrated that the further processing of
P47 is allelic type-dependent. The results of the present study would help in
vaccine designing based on SERA.
 
Insect Mol Biol  2002 Dec;11(6):517-25 
 
Genomic organization and regulation of three Cecropin genes in Anopheles
gambiae.
 
Zheng XL, Zheng AL.
 
The First Military Medical University, Department of Parasitology, Guangzhou,
The People's Republic of China; and Yale University School of Medicine,
Department of Epidemiology and Public Health, New Haven, CT, USA.
 
Three cecropin genes (AgCecA-C) were identified from Anopheles gambiae, a major
vector for malaria in sub-Saharan Africa. These genes form a cluster with AgCecA
and AgCecB positioned in opposite orientation, while AgCecC is downstream of
AgCecA in the same direction. One intron is present in each of these three
genes. Motif searches of promoter regions revealed elements that could be
regulated by the NF-kappaB family of transcriptional regulators. The divergent
promoter (1186 nucleotides in length) between CecA and CecB and the promoter for
CecC were analysed by transfection in An. gambiae cell lines. Results showed
that these promoters were up-regulated by lipopolysaccharide. The activity was
further elevated when heat-inactivated microbes were used to challenge the cell
line. At least one NF-kappaB site was required for inducible expression of both
CecA and CecB.
 
MMWR Surveill Summ  2002 Mar 29;51(1):15-28 
 
Malaria surveillance--United States, 1999.
 
Newman RD, Barber AM, Roberts J, Holtz T, Steketee RW, Parise ME.
 
Epidemic Intelligence Service, Epidemiology Program Office, USA.
 
PROBLEM/CONDITION: Malaria is caused by four species of intraerythrocytic
protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P.
malariae). Malaria is transmitted by the bite of an infective female Anopheles
sp. mosquito. The majority of malaria infections in the United States occur in
persons who have traveled to areas with ongoing transmission. In the United
States, cases can occur through exposure to infected blood products, by
congenital transmission, or locally through mosquitoborne transmission. Malaria
surveillance is conducted to identify episodes of local transmission and to
guide prevention recommendations for travelers. PERIOD COVERED: Cases with
onset of illness during 1999. DESCRIPTION OF SYSTEM: Malaria cases confirmed
by blood films are reported to local and state health departments by health-care
providers or laboratory staff. Case investigations are conducted by local and
state health departments, and reports are transmitted to CDC through the
National Malaria Surveillance System (NMSS). Data from NMSS serve as the basis
for this report. RESULTS: CDC received reports of 1,540 cases of malaria with an
onset of symptoms during 1999 among persons in the United States or one of its
territories. This number represents an increase of 25.5% from the 1,227 cases
reported for 1998. P. falciparum, P. vivax, P. malariae, and P. ovale were
identified in 46.0%, 30.7%, 4.6%, and 3.6% of cases, respectively. More than one
species was present in 12 patients (0.8% of total). The infecting species was
unreported or undetermined in 223 (14.5%) cases. The number of reported malaria
cases acquired in Africa increased 27.6% (n = 901), compared with 1998, and an
increase of 2.9% (n = 246) occurred in cases acquired in Asia, compared with
1998. Cases from the Americas increased by 19.7% (n = 274) from 1998. Of 831
U.S. civilians who acquired malaria abroad, 159 (19.1%) reported that they had
followed a chemoprophylactic drug regimen recommended by CDC for the area to
which they had traveled. Three patients became infected in the United States,
all through probable local mosquitoborne transmission. Five deaths were
attributed to malaria, all caused by P. falciparum. INTERPRETATION: The 25.5%
increase in malaria cases in 1999, compared with 1998, resulted primarily from
increases in cases acquired in Africa and the Americas. This increase is
possibly related to a change in the system by which states report to CDC, but it
could also have resulted from local changes in disease transmission, increased
travel to these regions, improved reporting to state and local health
departments, or a decreased use of effective antimalarial chemoprophylaxis. In
the majority of reported cases, U.S. civilians who acquired infection abroad
were not on an appropriate chemoprophylaxis regimen for the country where they
acquired malaria. PUBLIC HEALTH ACTIONS: Additional information was obtained
concerning the five fatal cases and the three infections acquired in the United
States. The NMSS surveillance form was modified to gather more detailed
information regarding compliance with prescribed chemoprophylaxis regimens.
Persons traveling to a malarious area should take one of the recommended
chemoprophylaxis regimens appropriate to the region of travel, and travelers
should use personal protection measures to prevent mosquito bites. Any person
who has been to a malarious area and who subsequently develops a fever or
influenza-like symptoms should seek medical care immediately; investigation
should include a blood-film test for malaria. Malaria infections can be fatal if
not diagnosed and treated promptly. Recommendations concerning prevention of
malaria can be obtained from CDC.
 
J Am Chem Soc  2002 Nov 13;124(45):13434-6 
 
Rapid synthesis of a glycosylphosphatidylinositol-based malaria vaccine 
using automated solid-phase oligosaccharide synthesis.
 
Hewitt MC, Snyder DA, Seeberger PH.
 
Contribution from the Department of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139.
 
Described is an automated synthesis of hexasaccharide malarial toxin 1,
currently under development as a malaria vaccine candidate. Using a combination
of automated solid-phase methods and solution-phase fragment coupling, the
target glycosylphosphatidylinositol was assembled in a matter of days, compared
with several weeks for a comparable solution-phase synthesis.
 
P N G Med J  2001 Mar-Jun;44(1-2):17-23 
 
Towards a malaria vaccine for Papua New Guinea.
 
Reeder JC.
 
Malaria is a major problem in Papua New Guinea, where it accounts for a high
proportion of sickness and death. In addition to the human suffering, malaria
also puts severe stress on the health services, and may directly hinder economic
growth. A malaria vaccine would be the best, most cost-effective and safest
public health measure to reduce the burden of malaria. Though considerable
technical challenges are present, much natural and scientific evidence suggests
a vaccine is achievable. Through the malaria vaccine program at the Papua New
Guinea Institute of Medical Research, Papua New Guinea is playing a significant
role in the global effort to develop a malaria vaccine, and ensuring that the
malaria patterns of the Asia-Pacific region figure strongly in vaccine
development strategies. Discussed here are some of the major issues to be
considered as we work towards a malaria vaccine for Papua New Guinea.
 
Biochem Biophys Res Commun  2002 Nov 1;298(3):371-6 
 
Molecular characterization and expression of an alternate proliferating cell
nuclear antigen homologue, PfPCNA2, in Plasmodium falciparum.
 
Patterson S, Whittle C, Robert C, Chakrabarti D.
 
Department of Molecular Biology and Microbiology, University of Central Florida,
32826, Orlando, FL, USA
 
The malaria parasite Plasmodium falciparum genome sequencing has revealed the
existence of a second gene for proliferating cell nuclear antigen (PCNA), a key
factor in a variety of DNA metabolic events. The alternate copy of PCNA
(PfPCNA2) shows only 23% identity to an earlier reported P. falciparum PCNA
homologue (PfPCNA1). Our analysis indicated structural conservation of PfPCNA2
compared to eukaryotic PCNAs. PfPCNA1 and 2 polypeptides showed differential
expression in the intraerythrocytic cell cycle of the malaria parasite. PfPCNA1
expression slowly increases about threefold from the ring to the late schizont
stage. In contrast PfPCNA2 showed robust expression in trophozoites and early
schizonts with a sudden drop in expression in the late schizont stage,
suggesting that the two PfPCNAs may function under different physiological
conditions. Chemical cross-linking indicated the presence of a trimeric PfPCNA2
protein, indicating the possible existence of a functional ring-like PfPCNA2
structure.
 
Blood  2002 Oct 31; [epub ahead of print] 
 
T cell activation and cytokine production via a bispecific single-chain 
antibody fragment targeted to blood-stage malaria parasites.
 
Yoshida S, Kobayashi T, Matsuoka H, Seki C, Gosnell WL, Chang SP, Ishii A.
 
A novel bispecific single-chain antibody fragment (biscFv) has been constructed
to address the possibility of a new approach to malaria therapeutic drug
development. The biscFv consists of two different single-chain antibody
fragments linked by a flexible peptide linker (Gly4-Ser)3. One of the two scFv
fragments is directed against a conserved epitope of the 19 kDa C-terminal
fragment of the major surface protein of human malignant malaria parasite,
Plasmodium falciparum, and the other is directed against the CD3 antigen of
human T cells. The biscFv expressed by a recombinant baculovirus retained the
antigen-binding properties of the corresponding univalent single-chain antibody
fragments and formed a bridge between P. falciparum and T cells. In cooperation
with T cells, the biscFv specifically induced not only IFN-gamma and TNF-alpha,
but also a significant increase of merozoite phagocytosis and growth inhibition
of P. falciparum in vitro. Thus, the biscFv possesses highly selective malaria
targeting properties and stimulates T cells to induce cytokines, presumably
resulting in activation of macrophages, neutrophils and NK cells and parasite
killing in vivo.
 
Zhonghua Yu Fang Yi Xue Za Zhi  2002 Mar;36(2):103-105 
 
GIS prediction model of malaria transmission in Jiangsu province.
 
Yang G, Zhou X, Malone J, McCarroll J, Wang T, Liu J, Gao Q, Zhang X, Hong Q,
Sun L.
 
Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China.
 
OBJECTIVES: To perform GIS spatial analysis on malaria transmission patterns in
Jiangsu after setting up a malaria database and developing GIS model of malaria
transmission in Jiangsu province. METHODS: The epidemiological GIS database of
malaria in Jiangsu province was established using ArcView 3.0a software. The
climate data covering Jiangsu province and its peripheral area were extracted
from the FAOCLIM database, the total growing degree days (TGDD) for Plasmodium
vivax were calculated, and spatial distribution for TGDD was analyzed by ArcVeiw
3.0a. RESULTS: The predicted malaria distribution map based on TGDD was created,
which showed that the transmission of malaria decreased gradually from west to
east, which can be divided into three belts according to the degree of
transmission. The 14-year mean morbidity distribution map of malaria in Jiangsu
showed that the middle and west parts of Jiangsu is the most serious endemic
area. The morbidity in the areas along the Taihu valley, such as Suzhou, Wuxi
and Changzhou, as well as Nantong and a few of northern counties are the lowest.
The morbidity of other places is at the middle level. The 14-year mean morbidity
distribution map of malaria is correlated with predicted malaria distribution
map for TGDD. CONCLUSION: It is possible to monitor the malaria transmission by
GIS predicted model based on TGDD.
 
Clin Infect Dis  2002 Nov 15;35(10):1147-54 
 
Efficacy of atovaquone/proguanil for malaria prophylaxis in children and its
effect on the immunogenicity of live oral typhoid and cholera vaccines.
 
Faucher JF, Binder R, Missinou MA, Matsiegui PB, Gruss H, Neubauer R, Lell B,
Que JU, Miller GB, Kremsner PG.
 
Medical Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon.
 
A double-blind, placebo-controlled study was conducted to measure the impact of
malaria prophylaxis with atovaquone/proguanil (A-P) on the immunogenicity of
vaccines against typhoid fever and cholera, Salmonella serotype Typhi Ty21a and
Vibrio cholerae CVD103-HgR, respectively. A total of 330 Gabonese schoolchildren
were assigned to receive either A-P or placebo for 12 weeks. Vaccination
occurred 3 weeks after the start of prophylaxis, and immunogenicity was assessed
4 weeks after vaccination. The protective efficacy of A-P against Plasmodium
falciparum malaria was of 97% (95% confidence interval, 79%-100%). The 2
treatment groups did not differ significantly with regard to changes in antibody
titers after vaccination (P=.96 for anti-S. Typhi IgG antibodies, P=.07 for
anti-S. Typhi IgA antibodies, and P=.64 for vibriocidal antibodies). The A-P
combination was highly effective for malaria prophylaxis, without interfering
with the in vivo immunogenicity of CVD103-HgR and Ty21a vaccines, and it could
therefore be simultaneously administered with these vaccines.
 
Nucleic Acids Res  2002 Nov 1;30(21):4607-17 
 
The malaria parasite Plasmodium falciparum encodes members of the Puf
RNA-binding protein family with conserved RNA binding activity.
 
Cui L, Fan Q, Li J.
 
Department of Entomology, The Pennsylvania State University, 501 ASI Building,
University Park, PA 16802, USA.
 
A novel class of RNA-binding proteins, Puf, regulates translation and RNA
stability by binding to specific sequences in the 3'-untranslated region of
target mRNAs. Members of this protein family share a conserved Puf domain
consisting of eight 36 amino acid imperfect repeats. Here we report two Puf
family member genes, PfPuf1 and PfPuf2, from the human malaria parasite
Plasmodium falciparum. Both genes are spliced with four and three introns
clustered within or near the Puf domains, respectively. Northern and RT-PCR
analysis indicated that both genes were differentially expressed in gametocytes
during erythrocytic development of the parasite. Except for similarities in the
Puf domain and expression profile, the deduced PfPuf1 and PfPuf2 proteins differ
considerably in size and structure. PfPuf1 has 1894 amino acids and a central
Puf domain, whereas PfPuf2 is much smaller with a C-terminal Puf domain. The
presence of at least two Puf members in other Plasmodium species suggests that
these proteins play evolutionarily similar roles during parasite development.
Both in vivo studies using the yeast three-hybrid system and in vitro binding
assays using the recombinant Puf domain of PfPuf1 expressed in bacteria
demonstrated intrinsic binding activity of the PfPuf1 Puf domain to the NRE
sequences in the hunchback RNA, the target sequence for Drosophila Pumilio
protein. Altogether, these results suggest that PfPufs might function during
sexual differentiation and development in Plasmodium through a conserved
mechanism of translational regulation of their target mRNAs.
 
Am J Trop Med Hyg  2002 Sep;67(3):230-2 
 
Cerebral involvement in benign tertian malaria.
 
Beg MA, Khan R, Baig SM, Gulzar Z, Hussain R, Smego RA Jr.
 
Department of Microbiology, The Aga Khan University Medical College, Karachi,
Pakistan. Email: [email protected]
 
Although Plasmodium vivax usually causes benign uncomplicated malaria, it can
occasionally result in severe disease with life-threatening, end-organ
involvement generally seen with falciparum malaria. We report a case of cerebral
malaria caused by P. vivax and review the literature on this subject.
 
Am J Trop Med Hyg  2002 Sep;67(3):225-9 
 
Pyrimethamine/sulfadoxine combination in the treatment of uncomplicated
falciparum malaria: relation between dihydropteroate synthase/dihydrofolate
reductase genotypes, sulfadoxine plasma levels, and treatment outcome.
 
Khalil I, Alifrangis M, Ronn AM, Gabar HA, Jelinek T, Satti GM, Bygbjerg IC.
 
Center for Medical Parasitology, Institute of Medical Microbiology and
Immunology, University of Copenhagen, Denmark. 
Email: [email protected]
 
Several in vitro studies have shown the correlation between mutations in dhfr
and dhps genes and resistance to pyrimethamine/sulfadoxine (PYR/SDX)
combination, but the in vivo correlates of these mutations with PYR/ SDX
efficacy have not been investigated fully. We assessed PYR/SDX efficacy in
relation to the frequency of dhfr and dhps mutations in 37 Plasmodium falciparum
isolates sampled before treatment. Plasma levels of SDX measured at days 0, 3,
7, and 14 ascertained drug absorption. Point mutations were detected only at
codons 51 and 108 of dhfr and codon 436 of dhps. The frequency of dhfr 51/108
and dhps 436 mutations was 79% and 8%. The plasma levels of SDX indicated
adequate drug absorption by all patients. The presence of Ile 51 and Asn 108
mutations among parasites that cleared after treatment indicates that these
mutations alone are insufficient to cause in vivo resistance. In all
recrudescent parasites, however, the presence of Ile 51/Asn 108 dhfr mutations
was coupled with the dhps Ala 436. The findings suggest that the presence of Ile
51/Asn 108 dhfr mutations and Ala 436 dhps confers decreased susceptibility of
P. falciparum to PYR/SDX in areas of low endemicity.
 
J Hered  2002 Jul-Aug;93(4):249-53 
 
Genetic Differentiation of Anopheles gambiae s.s. Populations in Mali, West
Africa, Using Microsatellite Loci.
 
Carnahan J, Zheng L, Taylor CE, Toure YT, Norris DE, Dolo G, Diuk-Wasser M,
Lanzaro GC.
 
Department of Organismic Biology, Ecology and Evolution, University of
California, Los Angeles, CA 90095-1606 (Carnahan, Taylor, and Diuk-Wasser).
 
Anopheles gambiae sensu stricto is a principal vector of malaria through much of
sub-Saharan Africa, where this disease is a major cause of morbidity and
mortality in human populations. Accordingly, population sizes and gene flow in
this species have received special attention, as these parameters are important
in attempts to control malaria by impacting its mosquito vector. Past measures
of genetic differentiation have sometimes yielded conflicting results, in some
cases suggesting that gene flow is extensive over vast distances (6000 km) and
is disrupted only by major geological disturbances and/or barriers. Using
microsatellite DNA loci from populations in Mali, West Africa, we measured
genetic differentiation over uniform habitats favorable to the species across
distances ranging from 62 to 536 km. Gene flow was strongly correlated with
distance (r(2) = 0.77), with no major differences among chromosomes. We conclude
that in this part of Africa, at least, genetic differentiation for
microsatellite DNA loci is consistent with traditional models of isolation by
distance.
 
Parasite Immunol  2002 Aug;24(8):395-9 
 
Relationship between reactive nitrogen intermediates and total 
immunoglobulin E, soluble CD21 and soluble CD23: comparison between
cerebral malaria and nonsevere malaria.
 
Nacher M, Singhasivanon P, Kaewkungwal J, Silachamroon U, Treeprasertsuk S,
Tosukhowong T, Vannaphan S, Looareesuwan S.
 
Unite INSERM 511, Immunobiologie Cellulaire et Moleculaire des Infections
Parasitaires, Faculte de Medecine Pitie-Salpetriere, Paris, France and Faculty
of Tropical Medicine, Mahidol University, Hospital for Tropical Diseases,
Bangkok, Thailand.
 
To search for evidence of a protective role of the CD23/NO pathway against
cerebral malaria, concentrations of reactive nitrogen intermediates (RNI) and
sCD21, total immunoglobulin (Ig)E and sCD23 were compared between 17 cases of
cerebral malaria and 33 controls. The geometric mean of sCD23 concentration was
higher among cerebral malaria cases than among controls (optical density
2643/1495, P = 0.01). The ratio between sCD21 and sCD23 was significantly lower
in cerebral malaria cases than in controls (0.67 +/- 0.02 versus 0.77 +/- 0.02,
respectively, P = 0.009). Multiple linear regression analysis showed that, among
cerebral malaria cases, there was a clear correlation between RNI and both IgE
(P = 0.007) and sCD21 (P < 0.0001). Among controls, there was a strong negative
correlation between RNI and sCD23 concentrations (r = -0.61, P < 0.0001).
However, multivariate analysis unmasked the fact that, in controls, there was
also a positive correlation between RNI and IgE (P = 0.045). Logistic regression
showed that increased RNI concentrations were associated with a cerebral malaria
adjusted odds ratio of 1.05 per unit increase [95% confidence interval (CI)
1.006-1.1, P = 0.02] and that an increased ratio between sCD21 and sCD23 was
associated with protection from cerebral malaria (adjusted OR = 0.00001 per unit
increase (95% CI 0-0.03, P = 0.005). These different immunological profiles
suggest that, among controls, the CD23/NO pathway was chronically stimulated
whereas, in cerebral malaria, its stimulation was acute, which could explain why
some patients developed cerebral malaria and others did not.
 
Parassitologia  2001 Dec;43(4):179-82 
 
Preliminary lack of evidence for simian odour preferences of savanna 
populations of Anopheles gambiae and other malaria vectors.
 
Costantini C, Diallo M.
 
Istituto Pasteur-Fondazione Cenci Bolognetti, Sezione di Parassitologia,
Dipartimento di Scienze di Sanita Pubblica, Universita di Roma La Sapienza,
Italy. Email: [email protected]
 
The behavioural response to several culicine and anopheline mosquitoes to the
odour of alternative hosts (human vs monkey) arranged in a choice set-up using
odour-baited entry traps (OBETs) was assessed in a field experiment in
south-eastern Senegal. The experimental protocol followed procedures analogous
to those adopted in olfactometer laboratory tests. Two adult Cercopithecus
aethiops and a child of similar mass slept inside separate tents and their
odours were drawn to each one of two paired OBETs so that approaching mosquitoes
could experience both odour-laden streams before "choosing" to fly against one
of the two air currents and into the trap. The traps were set up in a riverine
forest clearing near the town of Kedougou, where primates (Papio papio,
Cercopithecus aethiops, and Erythrocebus patas) are common. A total of 192
mosquitoes belonging to 4 genera was captured during 8 trap nights. All major
human malaria vectors including Anopheles gambiae sensu lato, An. funestus, and
An. nili, which constituted the bulk of the trap catch (N = 153), clearly
expressed a preference for human odour, with > 90% of captured mosquitoes 
caught in the human-baited trap. A sub-sample of specimens belonging to the
An. Gambiae complex caught in both traps was identified by rDNA-PCR and RFLP
as An. Gambiae sensu stricto molecular form S (7/10), and An. arabiensis (3/10).
The only species that did not show a preference for the alternative odour-laden air
streams, among those caught in significant numbers, were mosquitoes of the genus
Mansonia, with both Ma. uniformis and Ma. africana weakly preferring human
odour, but not at a statistically significant level. These results are in
accordance with the hypothesis that the strongly anthropophilic feeding
preferences of An. gambiae did not evolve from an ancestral association with
non-human primates.
 
J Infect Dis  2002 Nov 1;186(9):1371-1375 
 
Immunity to Placental Malaria. IV. Placental Malaria Is Associated with
Up-Regulation of Macrophage Migration Inhibitory Factor in Intervillous Blood.
 
Chaisavaneeyakorn S, Moore JM, Othoro C, Otieno J, Chaiyaroj SC, Shi YP, Nahlen
BL, Lal AA, Udhayakumar V.
 
Division of Parasitic Diseases, National Center for Infectious Diseases, Centers
for Disease Control and Prevention, Public Health Service, United States
Department of Health and Human Services, Atlanta, and Department of
Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
 
Macrophage migration inhibitory factor (MIF) may play a role in immune responses
to malaria during pregnancy by virtue of its ability to activate macrophages and
to overcome the immunosuppressive effect of glucocorticoids. The present study
investigated whether plasma MIF levels are altered in pregnant women with
placental malaria (PM) and/or human immunodeficiency virus (HIV) infection. For
the first time it is demonstrated that MIF levels in the intervillous blood
(IVB) plasma were significantly elevated, compared with that in both peripheral
plasma ( approximately 500-fold) and cord plasma (4.6-fold; P<.01). IVB
mononuclear cells also produced significantly higher levels of MIF, compared
with that of peripheral blood mononuclear cells. PM was associated with
increased levels of MIF in the IVB plasma (P<.02). Primigravid and secundigravid
women had significantly higher levels of MIF in their IVB plasma than did
multigravid women (P<.05). HIV infection did not significantly alter MIF levels
in any site examined.
 
J Infect Dis  2002 Nov 1;186(9):1321-9 
 
Opsonin-Independent Phagocytosis: An Effector Mechanism against Acute
Blood-Stage Plasmodium chabaudi AS Infection.
 
Su Z, Fortin A, Gros P, Stevenson MM.
 
Centre for the Study of Host Resistance, Research Institute of the McGill
University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
Email: [email protected]
 
Opsonin-independent macrophage phagocytosis was investigated as a possible
mechanism of controlling early blood-stage Plasmodium chabaudi AS infection.
Early during infection, peritoneal macrophages from resistant C57BL/6 (B6) mice
exhibited increased phagocytosis of parasitized red blood cells (pRBCs) and free
merozoites, which was absent in mice with deficient interferon (IFN)-gamma
production during infection, including susceptible A/J, interleukin (IL)-12 p40,
and IFN-gamma gene knockout mice. IFN-gamma treatment of macrophages 
collected from B6 and A/J mice early during infection enhanced phagocytosis of
pRBCs, but IL-10 treatment inhibited this function. In vitro and in vivo studies 
in which type I and II class A scavenger receptor-deficient mice and inhibitors of
scavenger and mannose receptors were used revealed that scavenger receptors
other than class A type I and II and mannose receptors may play a role in
malaria parasite uptake. These results indicate that opsonin-independent
phagocytosis contributes to the IFN-gamma-dependent control of acute blood-stage
malaria infection.