Social Sciences and
Soc Sci Med 2001 Apr;52(7):1043-55
Disease and dislocation: the impact of refugee movements on the
geography of malaria in NWFP, Pakistan.
- Kazmi JH, Pandit K
Department of Geography, University of Karachi, Pakistan.
- Email: [email protected]
Studies of the health implications of refugee movements have generally
focused on the effects of dislocation on the health of refugees and
the impacts on health care provision at the destination. A somewhat
more neglected aspect of the refugee-health research has been the
impact of refugee flows on the geography of disease, i.e., how the
spatial patterns of disease prevalence are modified through the influx
and settlement of refugee populations. We examine this issue by
examining the changing geography of malaria in Pakistan's North West
Frontier Province (NWFP) between 1972 and 1997. Until the late 1970s,
the highest incidence of malaria in the region was seen in the
southern and eastern parts. During the 1980s, however, two and a half
million Afghan refugees entered the NWFP and were housed in tented
villages along the border and in some interior areas. As the decade
progressed, there was a significant shift in the spatial pattern of
malaria, with the regions of highest incidence shifting to the west
and north, coinciding strongly with refugee concentrations. Our study
draws attention to the manner in which refugee influx and settlement
can alter the ecology of the disease system, leading to long-term
changes in the geography of malaria.
Trends Parasitol 2001 Mar 1;17(3):145-14
Child mortality and malaria
transmission intensity in Africa.
- Smith TA, Leuenberger R, Lengeler C
Swiss Tropical Institute, Socinstrasse 57, PO Box CH-4002, Basel,
The desirability of controlling malaria transmission in the areas of
highest endemicity of Plasmodium falciparum has long been debated.
Most recently, it has been claimed that rates of malaria morbidity are
no higher in areas of very high transmission in Africa than they are
in places with lower inoculation rates. We now review the literature
on the relationship of morbidity and mortality to malaria transmission
intensity, and have linked published child mortality and malaria
transmission rates to examine how age-specific mortality actually
varies with the inoculation rate of P. falciparum.
Trends Parasitol 2001 Mar 1;17(3):122-126
Possible modes of action of the
- Olliaro PL, Haynes RK, Meunier B, Yuthavong Y
UNDP/World Bank/WHO Special Programme on Research and Training in
Tropical Diseases, CDS Cluster, 20, avenue Appia, CH-1211, Geneva,
- Artemisinin-type compounds are used for the treatment of uncomplicated
and severe forms of malaria. They reduce parasitaemia more rapidly
than any other antimalarial compound known, and are effective against
multidrug-resistant parasites. However, uncertainties remain as to how
they act on the parasite and cause toxicity. In this review, we
summarize current ideas.
Mem Inst Oswaldo Cruz 2001 Feb;96(2):221
Protective CD8+ T cell responses
against the pre-erythrocytic stages of malaria parasites: an overview.
- Oliveira-Ferreira J, Daniel-Ribeiro C
Laboratorio de Pesquisas em Malaria, Instituto Oswaldo Cruz, Rio de
Janeiro, RJ, 21045-900, Brasil.
CD8+ T cells have been implicated as critical effector cells in
protection against the pre-erythrocytic stage of malaria in mice and
humans following irradiated sporozoite immunization. Immunization
experiments in animal models by several investigators have suggested
different strategies for vaccination against malaria and many of the
targets from liver stage malaria antigens have been shown to be
immunogenic and to protect mice from the sporozoite challenge. Several
prime/boost protocols with replicating vectors, such as vaccinia/influenza,
with non-replicating vectors, such as recombinant particles derived
from yeast transposon (Ty-particles) and modified vaccinia virus
Ankara, and DNA, significantly enhanced CD8+ T cell immunogenicity and
also the protective efficacy against the circumsporosoite protein of
Plasmodium berghei and P. yeti. Based on these experimental results
the development of a CD8+ T cell inducing vaccine has moved forward
from epitope identification to planning stages of safety and
immunogenicity trials of candidate vaccines.
Mem Inst Oswaldo Cruz 2001 Feb;96(2):179-184
Malaria vectors in the municipality
of Serra do Navio, State of Amapa, Amazon Region, Brazil.
- Povoa M, Wirtz R, Lacerda R, Miles M, Warhurst D
Secao de Parasitologia, Instituto Evandro Chagas, Funasa, Belem, PA,
We conducted a survey to determine the vectors of malaria in six
localities of Serra do Navio municipality, State of Amapa, from 1990
to 1991. Malaria infection rates of 29.3%, 6.2% and 20.4% were
detected by human blood smears in Colonia Agua Branca, Porto Terezinha
and Arrependido, respectively. There was no malaria infection detected
in Serra do Navio. Fifteen species were identified among 3,053
anopheline mosquitoes collected by human bait and 64.4% were
identified as Anopheles albitarsis s.l., 16.7% An. braziliensis, 9.5%
An. nuneztovari and 5.8% An. triannulatus. An. darlingi, the main
vector of malaria in the Amazon region of Brazil, was scare. Using
enzyme-linked immunosorbent assay (ELISA), a total positive rate of
0.8% (23/2876) was found for six species: fifteen An. albitarsis s.l.,
four An. nuneztovari, and one of each: An. braziliensis, An.
triannulatus, An. oswaldoi and An. rangeli. Nine of 23 positive
mosquitoes were infected with Plasmodium malariae, eight with P. vivax
VK210, three with P. vivax VK247 and three with P. falciparum. Since
An. albitarsis s.l. was collected feeding on humans, was present in
the highest density and was positive by ELISA for malaria sporozoites,
it probably plays an important role in malaria transmission in this
Mem Inst Oswaldo Cruz 2001 Jan;96(1):105-11
Characterization of constitutive and
putative differentially expressed mRNAs by means of expressed sequence
tags, differential display reverse transcriptase-PCR and randomly
amplified polymorphic DNA-PCR from the sand fly vector Lutzomyia
- Ramalho-Ortigao J, Temporal P, Oliveira Sd, Barbosa A, Vilela M,
Rangel E, Brazil R, Traub-Cseko Y
Departamento de Bioquimica e Biologia Molecular, Instituto Oswaldo
Cruz, Rio de Janeiro, RJ, 21045-900, Brasil.
Molecular studies of insect disease vectors are of paramount
importance for understanding parasite-vector relationship. Advances in
this area have led to important findings regarding changes in vectors'
physiology upon blood feeding and parasite infection. Mechanisms for
interfering with the vectorial capacity of insects responsible for the
transmission of diseases such as malaria, Chagas disease and dengue
fever are being devised with the ultimate goal of developing
transgenic insects. A primary necessity for this goal is information
on gene expression and control in the target insect. Our group is
investigating molecular aspects of the interaction between Leishmania
parasites and Lutzomyia sand flies. As an initial step in our studies
we have used random sequencing of cDNA clones from two expression
libraries made from head/thorax and abdomen of sugar fed L.
longipalpis for the identification of expressed sequence tags (EST).
We applied differential display reverse transcriptase-PCR and randomly
amplified polymorphic DNA-PCR to characterize differentially expressed
mRNA from sugar and blood fed insects, and, in one case, from a L.
(V.) braziliensis-infected L. longipalpis. We identified 37 cDNAs that
have shown homology to known sequences from GeneBank. Of these, 32
cDNAs code for constitutive proteins such as zinc finger protein,
glutamine synthetase, G binding protein, ubiquitin conjugating enzyme.
Three are putative differentially expressed cDNAs from blood fed and
Leishmania-infected midgut, a chitinase, a V-ATPase and a MAP kinase.
Finally, two sequences are homologous to Drosophila melanogaster gene
products recently discovered through the Drosophila genome initiative.
Biochem J 2001 Apr 15;355(Pt 2):333-338
Mechanism of malarial haem
detoxification inhibition by chloroquine.
- Pandey AV, Bisht H, Babbarwal VK, Srivastava J, Pandey KC, Chauhan
Malaria Research Group, International Center for Genetic Engineering
and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi 110067,
The haem detoxification pathway of the malaria parasite Plasmodium
falciparum is a potential biochemical target for drug development.
Free haem, released after haemoglobin degradation, is polymerized by
the parasite to form haemozoin pigment. Plasmodium falciparum
histidine-rich protein-2 (Pfhrp-2) has been implicated as the
catalytic scaffold for detoxification of haem in the malaria parasite.
Previously we have shown that a hexapeptide repeat sequence
(Ala-His-His-Ala-Ala-Asp), which appears 33 times in Pfhrp-2, may be
the major haem binding site in this protein. The haem binding studies
carried out by ourselves indicate that up to 18 equivalents of haem
could be bound by this protein with an observed K(d) of 0.94 ?M.
Absorbance spectroscopy provides evidence that chloroquine is capable
of extracting haem bound to Pfhrp-2. This was supported by the K(d)
value, of 37 nM, observed for the haem-chloroquine complex. The native
PAGE studies reveal that the formation of the haem-Pfhrp-2 complex is
disrupted by chloroquine. These results indicate that chloroquine may
be acting by inhibiting haem detoxification/binding to Pfhrp-2.
Moreover, the higher affinity of chloroquine for haem than Pfhrp-2
suggests a possible mechanism of action for chloroquine; it may remove
the haem bound to Pfhrp-2 and form a complex that is toxic to the
Br J Biomed Sci 2001;58(1):20-3
False-positive serological tests in
- Ghosh K, Javeri KN, Mohanty D, Parmar BD, Surati RR, Joshi SH
Institute of Immunohaematology (ICMR), 13th Floor, KEM Hospital MS
Building, Parel, Mumbai-400012, India.
Email: [email protected]
A range of serological tests, including rapid plasma reagin (RPR),
Widal test, enzyme-linked immunosorbent assay (ELISA) for human
immunodeficiency virus (HIV)-1 and -2, direct Coombs' test (DCT), and
rheumatoid factor (RF) were performed in a well-characterised cohort
of 100 patients with acute malaria (Plasmodium vivax infection: 31
patients; P. falciparum infection: 69 patients). Twenty-five healthy
volunteers from a similar area were used as controls. Three patients
from the severe P. falciparum group died, the remainder of the
patients recovered completely. A large proportion of these patients
showed false-positive serological reactions during the acute stage of
infection, which became negative on re-testing, four weeks after
recovery. In tropical countries such as India, where malaria is
endemic, results of serological tests should be interpreted with
caution in a patient with pyrexia of unknown origin (PUO)
Trends Parasitol 2001 Apr;17(4):194-7
Antibodies and Plasmodium falciparum
- Ramasamy R, Ramasamy M, Yasawardena S
Dept of Genetics, University of Groningen, Kerklaan 30, 9751 NN, Haren,
There is considerable interest in using merozoite proteins in a
vaccine against falciparum malaria. Observations that antibodies to
merozoite surface proteins block invasion are a basis for optimism.
This article draws attention to important and varied aspects of how
antibodies to Plasmodium falciparum merozoites affect red blood cell
Trends Parasitol 2001 Apr;17(4):189-94
Trade-offs, conflicts of interest and
manipulation in Plasmodium-mosquito interactions.
- Schwartz A, Koella JC
Department of Zoology, Aarhus University, Universitetsparken B135,
DK-8000, Aarhus, Denmark
A long-held view among parasitologists is that infection by malaria
parasites does not harm the mosquito vector. One of the reasons for
this belief is that the two partners of the association share
interests in the most important life-history traits of the mosquito.
Both partners benefit from increased survival and an increased rate of
bloodfeeding - the mosquito to increase its reproductive success and
the parasite to ensure its transmission. Problems with this line of
reasoning appear when one considers possible trade-offs among the
mosquito's life-history parameters, which constrain the attempts by
the mosquito and the parasite to maximize their success. Could these
constraints differ between the two partners and thus lead to conflicts
of interest and what would be the evolutionary and epidemiological
consequences of conflicting interests? These questions will be
Exp Parasitol 2001 Feb;97(2):61-9
Plasmodium falciparum: Immunogenicity
of Alum-Adsorbed Clinical-Grade TBV25-28, a Yeast-Secreted Malaria
Transmission-Blocking Vaccine Candidate.
- Gozar MM, Muratova O, Keister DB, Kensil CR, Price VL, Kaslow DC
Malaria Vaccines Section, National Institutes of Health, Bethesda,
Maryland, 20892, U.S.A.
- Gozar, M. M. G., Muratova, O., Keister, D. B., Kensil, C. R., Price,
V. L., and Kaslow, D. C. 2001. Plasmodium falciparum: Immunogenicity
of alum-adsorbed clinical-grade TBV25-28, a yeast-secreted malaria
transmission-blocking vaccine candidate. Experimental Parasitology 97,
61-69. The fusion of Pfs25 and Pfs28, two major surface antigens on
zygotes and ookinetes of Plasmodium falciparum, as a single
recombinant protein (TBV25-28) was previously shown to elicit potent
transmission-blocking antibodies in mice. Clinical-grade TBV25-28 was
subsequently manufactured and its potency was evaluated in rabbits.
Rabbits received three doses of either clinical-grade TBV25H or
clinical-grade TBV25-28 adsorbed to alum with or without QS-21. As
measured in a standard membrane-feeding assay, addition of QS-21 to
the formulations appeared to enhance transmission-blocking potency of
rabbit sera after two vaccinations but not after three vaccinations.
Surprisingly, TBV25H elicited more potent transmission-blocking
antibodies than did TBV25-28, a result strikingly different from those
of previous mouse experiments using research-grade TBV25-28. The
apparent decrease in potency of clinical-grade TBV25-28 in rabbits
appears to reflect an enhancement in potency of clinical-grade TBV25H
in a new formulation rather than simply a species difference in
immunogenicity of TBV25-28. Copyright 2001 Academic Press.
Trans R Soc Trop Med Hyg 2001 Jan-Feb;95(1):7-13
Area effects of bednet use in a malaria-endemic area in Papua New
- Hii JL, Smith T, Vounatsou P, Alexander N, Mai A, Ibam E, Alpers MP
Guinea Institute of Medical Research, P.O. Box 378, Madang, Papua New
Guinea. Email: [email protected]
Relationships between area coverage with insecticide-free bednets and
prevalence of Plasmodium falciparum were investigated in 7
community-based surveys over a 33-month period in 1990-93 in 6
villages in the Wosera area of Papua New Guinea. Spatial patterns in
circumsporozoite rates for P. falciparum, P. vivax isomorphs K210 and
K247, and P. malariae, and the proportions of mosquito blood meals
positive for specific human, goat, cat, dog and pig antigens were
determined using ELISAs. P. falciparum prevalence in humans was better
explained by bednet coverage in the immediate vicinity than by
personal protection alone. Circumsporozoite rates for both P.
falciparum and P. vivax were also inversely related to coverage with
bednets. There was some increase in zoophagy in areas with high
coverage, but relatively little effect on the human blood index or on
overall mosquito densities. In this setting, protracted use of
untreated bednets apparently reduces sporozoite rates, and the
associated effects on prevalence are greater than can be accounted for
by personal protection. Even at high bednet coverage most anophelines
feed on human hosts, so the decreased sporozoite rates are likely to
be largely due to reduction of mosquito survival. This finding
highlights the importance of local vector ecology for outcomes of
bednet programmes and suggests that area effects of untreated bednets
should be reassessed in other settings.
Trans R Soc Trop Med Hyg 2001 Jan-Feb;95(1):50-5
The comparative efficacy of chloroquine and
sulfadoxine-pyrimethamine for the treatment of uncomplicated
falciparum malaria in Kampala, Uganda.
- Kamya MR, Dorsey G, Gasasira A, Ndeezi G, Babirye JN, Staedke SG,
Department of Medicine, Makerere University, P.O. Box 7072, Kampala,
Uganda. Email: [email protected]
Chloroquine (CQ) remains the first-line treatment for uncomplicated
malaria in much of Africa despite the growing problem of resistance to
this drug. Sulfadoxine-pyrimethamine (SP) is often used after CQ
treatment failure and has replaced CQ as the first-line treatment in
parts of Africa. To compare the efficacy of these 2 regimens, we
evaluated, in March-August 1999, clinical and parasitological
responses over 28 days in 214 children and adults from Kampala,
Uganda, with uncomplicated falciparum malaria. Compared to SP,
significantly more patients treated with CQ developed early or late
clinical failure (54% vs 11%, P < 0.001) and parasitological
failure (72% vs 30%, P < 0.001) during 14 days of follow-up. The
risk of treatment failure occurring after day 14 was similar between
the 2 treatment groups. Among those treated with CQ, children aged
< 5 years were at higher risk of clinical failure than older
individuals (76% vs 28%, P < 0.001), an association not seen with
SP (11% vs 10%, P = 0.91). Although early parasite clearance was
significantly better in the SP group (P = 0.001), fever clearance at
day 3 was the same (CQ 85%, SP 86%). These and other recent findings
suggest that consideration be given to replacing CQ as the first-line
therapy for uncomplicated malaria in Uganda, particularly in young
Trans R Soc Trop Med Hyg 2001 Jan-Feb;95(1):
Malaria in the highlands of Madagascar after five years of indoor
house spraying of DDT.
- Jambou R, Ranaivo L, Raharimalala L, Randrianaivo J, Rakotomanana
F, Modiano D, Pietra V, Boisier P, Rabarijaona L, Rabe T, Raveloson N,
De Giorgi F
Pasteur Institute of Madagascar, Madagascar.
- Email: [email protected]
The central region of Madagascar is a vast area of highlands (altitude
700-2000 m). Malaria transmission has re-established itself here since
the last epidemic of 1985-90 and has caused the deaths of 40,000
persons according to the Minister of Health. To combat the main
malaria vector in the region, Anopheles funestus, annual programmes of
indoor house spraying of DDT were carried out between December 1993
and January 1998 in most rural areas at altitude 1000-1500 m. A
parasitological and serological study was then conducted in the
highland schools to evaluate the impact of the programme and set up a
database on the region. Using a cluster-sampling method 2 independent
selections were conducted (one of 130 sites, the other of 40 sites).
During the study, 13,462 schoolchildren were examined, 71% living in
sprayed villages. Parasite prevalence among schoolchildren declined as
altitude increases, from 11% at 700-900 m to 0.4% at > 1500 m.
Below 1500 m, the impact of the spraying on the prevalence of the
parasite was very clear (an average decrease of from 20% to 2.7% below
1000 m and of from 4.5% without spraying to 0.8% at 1000-1500 m).
Geographical analysis of the data showed that the marginal regions
remained the most affected by malaria (especially outside spraying
zones), and persistence of 'pockets of transmission' at 1000-1500 m,
essentially in areas where spraying has never been used. In 9 schools,
anti-Plasmodium antibodies were sought by indirect immunofluorescence
on thick smears of parasitized red blood cells. The seroprevalence
ranged from 22% to 63%, which suggests that the parasite is still
circulating in the region. Even though our data show that vector
control continues to be very successful in the Madagascan highlands,
rapid reinfection could occur and must be monitored following
spraying. To this end, the Minister for Health, with the support of
the Italian Co-operation, has placed the region under epidemiological
surveillance since 1997. An alert system for the timely detection of
the sources of epidemics and the targeting of the antivectoral
campaign is also in operation. Our study suggests that this strategy
should be reinforced by the spraying of DDT in the marginal zones in
order to consolidate the results obtained at higher altitudes.
Trans R Soc Trop Med Hyg 2001 Jan-Feb;95(1):1-6
Associations of peak shifts in age--prevalence for human malarias
with bednet coverage.
- Smith T, Hii JL, Genton B, Muller I, Booth M, Gibson N, Narara A,
Papua New Guinea Institute of Medical Research, P.O. Box 378, Madang,
Papua New Guinea.
Email: [email protected]
Effects of bednet coverage (C) on prevalence of malaria were analysed
using data from 1990-92 from 9 Papua New Guinean villages. Effects of
coverage varied by age, resulting in a shift in age of peak prevalence
from 4.7 (C = 0%) to 11.6 (C = 100%) years for Plasmodium falciparum,
from 3.4 to 4.9 years for P. vivax and from 11.0 to 16.8 years for P.
malariae. In small areas with no bednets the age distribution of P.
falciparum parasitaemia was like that of a holoendemic area. Where
coverage was complete the pattern corresponded to mesoendemicity.
Thus, protracted use of bednets can result in profound changes in the
endemicity of malaria even when coverage is incomplete and without
insecticide treatment. Average entomological inoculation rates (EIRs)
estimated from indoor landing rates on individuals without bednets
were 35, 12 and 10 infectious bites per person per annum for P.
falciparum, P. vivax and P. malariae, respectively. Logistic
regression analyses indicated that the EIR estimate for P. falciparum
was related to prevalence of this species independently of effects of
bednet coverage. However, the recent EIR still accounted for much less
variation than did the bednets. A similar pattern was seen for P.
malariae, while there were no significant relationships between the
recent EIR and the parasite positivity for P. vivax. It is concluded
that short-term variations in inoculation rate are not important
determinants of parasite prevalence in this population.
Bioorg Med Chem Lett 2001 Mar 26;11(6):761-4
Peptidomimetic inhibitors of protein farnesyltransferase show
potent antimalarial activity.
- Ohkanda J, Lockman JW, Yokoyama K, Gelb MH, Croft SL, Kendrick H,
Harrell MI, Feagin JE, Blaskovich MA, Sebti SM, Hamilton AD
Department of Chemistry, Yale University, New Haven, CT 06520, USA.
Malaria continues to represent a very serious health problem in the
tropics. The current methods of clinical treatment are showing
deficiencies due to the increased incidence of resistance in the
parasite. In the present paper we report the design, synthesis, and
evaluation of potential antimalarial agents against a novel target,
protein farnesyltransferase. We show that the most potent compounds
are active against Plasmodium falciparum in vitro at submicromolar
Trends Immunol 2001 Apr;22(4):171-2
Immunology, climate change and vector-borne
- Patz JA, Reisen WK
Program on Health Effects of Global Environmental Change, Dept of
Environmental Health Sciences, Johns Hopkins School of Hygiene and
Public Health, 615 N. Wolfe St, 21205, Baltimore, MD, USA
Global climate change might expand the distribution of vector-borne
pathogens in both time and space, thereby exposing host populations to
longer transmission seasons, and immunologically naive populations to
newly introduced pathogens. In the African highlands, where cool
temperatures limit malaria parasite development, increases in
temperature might enhance malaria transmission. St Louis encephalitis
viral replication and the length of the transmission season depend
upon ambient temperature. Warming temperatures in the American
southwest might place at risk migratory, non-immune elderly persons
that arrive in early fall to spend the winter. Warm temperatures might
intensify or extend the transmission season for dengue fever.
Immunologists should examine this interplay between human
immunocompetence and vector-borne disease risks in a warmer world.
Physiol Rev 2001 Apr;81(2):495-537
Membrane transport in the malaria-infected erythrocyte.
- Kirk K
Division of Biochemistry and Molecular Biology, Faculty of Science,
Australian National University, Canberra, Australian Capital
The malaria parasite is a unicellular eukaryotic organism which,
during the course of its complex life cycle, invades the red blood
cells of its vertebrate host. As it grows and multiplies within its
host blood cell, the parasite modifies the membrane permeability and
cytosolic composition of the host cell. The intracellular parasite is
enclosed within a so-called parasitophorous vacuolar membrane, tubular
extensions of which radiate out into the host cell compartment. Like
all eukaryote cells, the parasite has at its surface a plasma
membrane, as well as having a variety of internal membrane-bound
organelles that perform a range of functions. This review focuses on
the transport properties of the different membranes of the
malaria-infected erythrocyte, as well as on the role played by the
various membrane transport systems in the uptake of solutes from the
extracellular medium, the disposal of metabolic wastes, and the origin
and maintenance of electrochemical ion gradients. Such systems are of
considerable interest from the point of view of antimalarial
chemotherapy, both as drug targets in their own right and as routes
for targeting cytotoxic agents into the intracellular parasite.
J Assoc Physicians India 1998 Apr;46(4):360-2
The changed clinical spectrum of malaria due to drug resistance.
Mehta SR, Kohle VS, Chauhan SS
Medical Division, Army Hospital (Referral and Research), Delhi
The clinical spectrum of 14 cases of Plasmodium falciparum malaria
(PF) who received empirical treatment and suffered from initial
prolonged mild illness culminating into severe complicated malaria are
presented. The empirical treatment (ET) consisted of adequate doses of
chloroquine in 9, chloroquine with pyrimethamine-sulphadoxine
combination in 3 and pyrimethamine-sulphadoxine alone in 2 cases.
Moderate fever and weakness persisted for 7 to 28 days leading to
anaemia and progressive hepatosplenomegaly in all patients. Other
clinical features noticed included jaundice in 5, sudden shock with
pulmonary oedema in 4, cerebral malaria and renal failure in 3 each
and multiorgan in 4 cases. Subsequent investigations revealed PF rings
in 9 cases, mixed PF and vivax infection in 3 and PF gametocytaemia
only in 2 patients. Seven patients received quinine, 4 quinine with
doxycycline and 3 were given quinine followed by injection artemether.
Exchange transfusion was carried out in two cases. Four patients died.
The empirical treatment with first line antimalarials alters the
clinical profile of resistant PF, makes it milder temporarily, delays
in confirming the diagnosis and leads to high mortality. There is
urgent need for more diligent early workup for these patients who
linger on with moderate pyrexia, progressive hepatosplenomegaly,
anaemia and jaundice after ET till better diagnostic methods are
available to avoid the prolonged illness and high mortality.
J Assoc Physicians India 2000 May;48(5):473-7
Prognostic significance of eye changes in cerebral malaria.
- Kochar DK, Shubhakaran, Kumawat BL, Vyas SP
Department of Medicine, Divisionof Neurology, SP Medical College,
AIMS: Eye in Plasmodium falciparum malaria are described by various
workers all over the world but its prognostic significance is not
clear because of conflicting observation by different authors from
different regions. No such study is available on Indian adult patients
of cerebral malaria. So we want to describe our observations on
various eye abnormalities in these patients and study its prognostic
significance. METHODOLOGY: Two hundred and fourteen adult (> 14
years) patients of strictly defined cerebral malaria admitted in
classified malaria ward in this tertiary level health care station
were studies. Detailed ophthalmoscopic examination was done through
dilated pupils at the time of admission, daily thereafter, at the time
of discharge and at weekly intervals in those with persistent changes
at the time of discharge. RESULT: Retinal haemorrhage was found in 25
(11.68%) patients, papilloedema in 17 (7.94%), blurring of disc
margins in 25 (11.68%), retinal oedema in six (2.8%), disc pallor in
five (2.33%), vitreous haemorrhage and hard exudate in one (0.46%)
each and subconjunctival haemorrhage in six (2.8%) patients. The
mortality associated with individual finding was not statistically
significant except disc pallor. CONCLUSION: None of the above finding
except disc pallor (p < 0.05) was associated with statistically
significant mortality (p > 0.05); whereas any of the fundus
findings as a whole was related to statistically significant mortality
(p < 0.05).
Parasitology 2001 Feb;122(Pt 2):233-51
Methods for estimation of associations between multiple species
- Howard SC, Donnell CA, Chan MS
Wellcome Trust Centre for the Epidemiology of Infectious Disease,
Department of Zoology, University of Oxford, UK.
Email: [email protected]
Human populations are often infected with more than one species of
parasite, especially in developing countries where overall rates of
parasitism are high. Infections with multiple parasite species may not
necessarily be independent within an individual as physiological,
immunological or ecological factors may result in positive or negative
associations between infections with different parasite species. A
general framework for estimation of these associations is presented.
Data from over 215000 individuals are analysed and the associations
between geohelminth (Ascaris lumbricoides, Trichuris trichiura and
hookworm) and malaria species are investigated. A method is presented
for analysing data from multiple communities and testing whether the
associations in different communities are equal. Overall estimates of
the associations between species are obtained for each country and
continent where data were available. Associations between geohelminth
species were, in general, found to be positive whilst both positive
and negative associations were found between the different Plasmodium
species. There was evidence for significant geographical heterogeneity
between the associations. A method for using these parameter estimates
to predict the distribution of multiple infections when only marginal
prevalence data are available is described and demonstrated.
Paediatr Drugs 2001;3(2):113-21
Antimalarial chemoprophylaxis in infants and children.
- Kramer MH, Lobel HO
Division of Parasitic Diseases, National Center for Infectious
Diseases, Centers for Diseases Control and Prevention, Atlanta,
Georgia 30341, USA.
The evolving patterns of drug resistance in malaria parasites and
changes in recommendations for malaria prevention present a challenge
to physicians who advise travellers on chemoprophylaxis. Because
compliance with personal protection measures is usually low, children
should receive appropriate chemoprophylaxis, including breast-fed
infants who are not protected through maternal chemoprophylaxis. For
travel to areas where chloroquine resistance has not yet been reported
(i.e. parts of Central America, the Caribbean and parts of the Middle
East), chloroquine alone is sufficient for antimalarial prophylaxis.
Mefloquine is the drug of choice for chemoprophylaxis in areas with
chloroquine-resistant Plasmodium falciparum, and can be given to
infants and young children. The combination of chloroquine and
proguanil is well tolerated in children but is much less effective
against drug-resistant malaria. Further research is needed to
determine the best dosage regimen for antimalarial drugs used for
chemoprophylaxis in children.
Parasitol Int 1999 Aug;48(2):157-67
Suppressed expression of hypoxanthine-guanine
phosphoribosyltransferase (HGPRT) in an irradiation-attenuated
Plasmodium berghei XAT strain.
- Onda T, Miyamoto K, Sugioka Y, Kangawa K, Kano S, Suzuki M
Department of Parasitology, Gunma University School of Medicine,
Plasmodium berghei XAT (XAT) is a non-reversible, non-lethal type
malaria parasite strain derived from the highly virulent lethal P.
berghei NK65 (NK65) by X-irradiation. The difference in polypeptide
expression between NK65 and XAT was examined in this study. Western
blot patterns of the parasite polypeptides showed that a 30-kDa
polypeptide was not detected in XAT. In the present paper, we focused
the study on the difference in the expression of the 30-kDa
polypeptide between XAT and NK65. Although several other significant
differences were noted in the spots shown by two-dimensional gel
electrophoresis, the 30-kDa polypeptide was isolated by means of
preparative 2D-gel electrophoresis followed by HPLC, and N-terminal
amino acid sequence of the polypeptide was eventually determined.
Complementary DNA clones encoding the 30-kDa polypeptide were isolated
and characterized. Full-length cDNA clones from XAT encoded a protein
of 231 amino acid residues with a 693-bp open reading frame. The
deduced amino acid sequence exhibited 67% identity with that for P.
falciparum hypoxanthine-guanine phosphoribosyltransferase (HGPRT; EC
220.127.116.11), suggesting that this protein is P. berghei HGPRT. Northern
blot analysis revealed that expression of HGPRT in XAT was only
one-eighth of that in NK65. This finding indicates that HGPRT gene
expression is markedly suppressed in XAT. The amino acid sequence of
HGPRT from NK65 was identical to that from XAT. This finding showed
that the amino acid sequence of XAT-HGPRT was not mutated and had not
J Med Entomol 2001 Jan;38(1):22-8
Effects of available sugar on the reproductive fitness and
vectorial capacity of the malaria vector Anopheles gambiae (Diptera:
- Gary RE Jr, Foster WA
Department of Entomology, the Ohio State University, 1735 Neil Avenue,
Columbus, OH 43210, USA.
Although females of most mosquito species are known to use sugar as a
necessary source of energy, female Anopheles gambiae Giles sensu
stricto are thought to use it facultatively or not at all. However,
field evidence of sugar-free living is inconclusive, and the
implications for reproductive fitness and vectorial capacity are
unknown. To evaluate the role that sugar may play in the ecology of
these mosquitoes, mated female An. gambiae in the laboratory were
given access to either no food (water only), 10% sucrose, human blood,
or human blood + 10% sucrose, and comparisons of daily mortality,
fecundity, and biting frequency were made. The effect of sugar
availability on vectorial capacity and the intrinsic rate of increase,
a measure of fitness, then were determined. Females (pooled and
individual) given blood + sugar lived significantly longer than did
those on the other diets. Daily fecundity was higher for females given
blood alone than for those fed blood + sugar (13 versus 9 eggs per
female daily). However, total fecundity and intrinsic rate of increase
were not affected by sugar availability. Biting frequency was
significantly higher (0.41 versus 0.26 bites per female per day) for
females given blood alone. Despite the reduced survivorship, exclusive
blood-feeding led to a theoretically higher vectorial capacity for
Plasmodium falciparum at 27 degrees C. These data indicate that female
An. gambiae could replace sugar with increased blood feeding without
suppressing reproductive fitness. Increased blood feeding could, in
turn, increase the rate of malaria transmission and may explain the
unusual efficiency of this vector.
J Med Entomol 2001 Jan;38(1):122-5
Dogs as a favored host choice of Anopheles gambiae sensu stricto (Diptera:
Culicidae) of Sao Tome West Africa.
- Sousa CA, Pinto J, Almeida AP, Ferreira C, do Rosario VE, Charlwood
Unidade de Entomologia Medica, Instituto de Higiene e Medicina
Tropical, Universidade Nova de Lisboa. Rua da Junqueira 96, 1349-008
The host source and human blood index (HBI) of an exophilic population
of the "forest" cytoform of Anopheles gambiae Giles sensu
stricto, from a peri-urban area of the island of Sao Tome were
assessed. Blood meals of 434 An. gambiae females from all-night indoor
light-trap collections, 193 from indoor and 422 from outdoor resting
collections, were determined by ELISA. Significant differences were
found in the HBI estimates from insects collected indoors (0.93) and
outdoors (0.27). Blood-fed insects collected resting outdoors provided
the most representative sample for host determination. Dogs were the
predominant hosts, followed by humans and pigs. Of all human feeds, it
was estimated that 81.5% were taken inside houses. The low HBI of 0.27
for the An. gambiae population explains the low sporozoite rate and
the meso-endemicity of malaria in the island.
Parasitol Int 2001 Mar;50(1):33-9
A potent antimalarial activity of Hydrangea macrophylla var. Otaksa
leaf extract against Plasmodium yoelii 17XL in mice.
- Ishih A, Ikeya C, Yanoh M, Takezoe H, Miyase T, Terada M
Department of Parasitology, Hamamatsu University School of Medicine,
3600 Handa-cho, 431-3192, Hamamatsu, Japan
The antimalarial activity of the hot-water extract of Hydrangea
macrophylla var. Otaksa leaves was evaluated against Plasmodium yoelii
17XL in mice. Non-treated control mice died from 6 to 7 days after
infection, but mice treated with the leaf extract survived during the
experiment. Mice given the extract orally showed low parasitemia
levels during administration. Following a transient recrudescence of
malaria parasites in the bloodstream of treated mice, no parasites
could be detected by a microscopic examination. Furthermore, the 30%
MeOH aq. eluate and 50% MeOH aq. eluate from dried leaves of H.
macrophylla var. Otaksa showed an antimalarial activity in vivo.
Sulfamonomethoxine was orally given to infected mice to compare with
the antimalarial activity of the hot-water extract of leaves.
Sulfamonomethoxine given orally reduced parasitemia, but no complete
cure of mice was observed.
Parasitol Int 2001 Mar;50(1):9-13
Variation of incubation time in an in vitro drug susceptibility
test of Plasmodium falciparum isolates studied in the Solomon Islands.
- Inaba H, Ohmae H, Kano S, Faarado L, Boaz L, Leafasia J, Suzuki M
Department of Parasitology, Gunma University School of Medicine,
3-39-22 Showa-machi, Maebashi, Gunma, Japan
A study on chloroquine resistance of falciparum malaria was conducted
in the Solomon Islands. Both in vitro and clinical tests were
performed. In our regular studies of in vitro chloroquine
susceptibility tests on Plasmodium falciparum from non-immuners in
Japan, the threshold point to differentiate resistant and susceptible
isolates was set at a 0. 114 ?M chloroquine in the semi-micro culture
system, and this point was also applicable in the study of the malaria
parasite taken in the highly endemic malarious area with good
coincidence with clinical observation. Variation in the incubation
time (24-63) to reach the schizont stage of the isolated parasites
were noted. It appeared that chloroquine resistant P. falciparum
showed traits to reach the schizont stage within a shorter incubation
Emerg Infect Dis 2001 Jan-Feb;7(1):35-42
Geographic subdivision of the range of the malaria parasite
- Li J, Collins WE, Wirtz RA, Rathore D, Lal A, McCutchan TF
National Institutes of Health, Bethesda, Maryland, USA.
We examined geographically distinct isolates of Plasmodium vivax and
categorized them according to developmental success in Anopheles
albimanus. We found that parasites from Central America and Colombia
form a group distinct from those of Asia. New World isolates have a
distinct chromosomal translocation and an episomal variation in the
open reading frame (ORF) 470 DNA sequence that distinguishes them from
the other isolates tested. Old World types of P. vivax were introduced
into the Americas, and a remnant of this lineage remains in P. simium.
It is indistinguishable from Old World P. vivax to the extent
determinable by using our encoded markers and the examination of its
developmental pattern in mosquitoes. The cohesive characteristics that
separate types of P. vivax are predictors of range and potential for
transmission and hence require taxonomic distinction.
Immunol Cell Biol 2001 Apr;79(2):101-20
Central nervous system in cerebral malaria: 'Innocent bystander' or
active participant in the induction of immunopathology?
- Medana IM, Chaudhri G, Chan-Ling T, Hunt NH
Departments of Pathology and Anatomy/Histology, University of Sydney,
New South Wales, Australia.
Cerebral malaria (CM) is a major life-threatening complication of
Plasmodium falciparum infection in humans, responsible for up to 2
million deaths annually. The mechanisms underlying the fatal cerebral
complications are still not fully understood. Many theories exist on
the aetiology of human CM. The sequestration hypo-thesis suggests that
adherence of parasitized erythrocytes to the cerebral vasculature
leads to obstruction of the microcirculation, anoxia or metabolic
disturbances affecting brain function, resulting in coma. This
mechanism alone seems insufficient to explain all the known features
of CM. In this review we focus on another major school of thought,
that CM is the result of an over-vigorous immune response originally
evolved for the protection of the host. Evidence in support of this
second hypothesis comes from studies in murine malaria models in which
T cells, monocytes, adhesion molecules and cytokines, have been
implicated in the development of the cerebral complications. Recent
studies of human CM also indicate a role for the immune system in the
neurological complications. However, it is likely that multiple
mechanisms are involved in the induction of cerebral complications and
both the presence of parasitized erythrocytes in the central nervous
system (CNS) and immunopathological processes contribute to the
pathogenesis of CM. Most studies examining immunopathological
responses in CM have focused on reactions occurring primarily in the
systemic circulation. However, these also do not fully account for the
develop-ment of cerebral complications in CM. In this review we
summarize results from human and mouse studies that demonstrate
morphological and functional changes in the resident glial cells of
the CNS. The degree of immune activation and degeneration of glial
cells was shown to reflect the extent of neurological complications in
murine cerebral malaria. From these results we highlight the need to
consider the potentially important contribution within the CNS of glia
and their secreted products, such as cytokines, in the development of
J Infect Dis 2001 Apr 15;183(8):1260-8
Malaria infection induces virus expression in human
immunodeficiency virus transgenic mice by cd4 t cell-dependent immune
- Freitag C, Chougnet C, Schito M, Near KA, Shearer GM, Li C,
Langhorne J, Sher A
Immunobiology Section, Laboratory of Parasitic Diseases, National
Institute of Allergy and Infectious Diseases, and 4Howard Hughes
Medical Institute, Research Scholars Program, National Institutes of
Health, Bethesda, Maryland, USA.
To test the capacity of malaria parasites to trigger virus expression
in vivo, human immunodeficiency virus (HIV) transgenic mice were
infected with Plasmodium chabaudi chabaudi clone AS. Splenocytes
recovered during peak parasitemia showed a dramatic elevation in viral
p24 production that returned to baseline by day 15 and failed to
rebound at recrudescence or after reinfection. The major sources of
virus expression were antigen-presenting cells (APCs) rather than T
lymphocytes. Nevertheless, T cells from infected mice stimulated with
plasmodial antigen triggered 5-10-fold increases in p24 production
from dendritic cells in vitro, which suggests that viral induction
stems from interaction of malaria-specific T lymphocytes with
HIV-expressing APCs. Indeed, depletion of CD4 T cells resulted in a
70% reduction in the p24 response stimulated by malaria in vivo. These
findings demonstrate the ability of Plasmodium species to
immunologically activate latently integrated HIV in vivo but suggest
that this process may be restricted to acute infection.
J Infect Dis 2001 Apr 15;183(8):1254-9
Artesunate Reduces but Does Not Prevent Posttreatment Transmission
of Plasmodium falciparum to Anopheles gambiae.
- Targett G, Drakeley C, Jawara M, von Seidlein L, Coleman R, Deen J,
Pinder M, Doherty T, Sutherland C, Walraven G, Milligan P
Department of Infectious and Tropical Diseases, London School of
Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.
Email: [email protected]
Combination therapy that includes artemisinin derivatives cures most
falciparum malaria infections. Lowering transmission by reducing
gametocyte infectivity would be an additional benefit. To examine the
effect of such therapy on transmission, Gambian children with
Plasmodium falciparum malaria were treated with standard regimens of
chloroquine or pyrimethamine-sulfadoxine alone or in combination with
1 or 3 doses of artesunate. The infectivity to mosquitoes of
gametocytes in peripheral blood was determined 4 or 7 days after
treatment. Infection of mosquitoes was observed in all treatment
groups and was positively associated with gametocyte density. The
probability of transmission was lowest in those who received
pyrimethamine-sulfadoxine and 3 doses of artesunate, and it was 8-fold
higher in the group that received pyrimethamine-sulfadoxine alone.
Artesunate reduced posttreatment infectivity dramatically but did not
abolish it completely. The study raises questions about any policy to
use pyrimethamine-sulfadoxine alone as the first-line treatment for
Cell Microbiol 2001 Mar;3(3):125-131
Molecular mechanisms of Plasmodium falciparum placental
- Scherf A, Pouvelle B, Buffet PA, Gysin J
Unite de Biologie des Interactions Hote-Parasite, CNRS URA 1960,
Institut Pasteur, 25 rue du Dr Roux, 75724 Paris, France; Laboratoire
de Parasitologie Experimentale, Faculte de Medecine, Universite de la
Mediterranee (Aix-Marseille II), 13385 Marseille Cedex 5, France.
In natural Plasmodium falciparum infections, parasitized erythrocytes
(PEs) circulate in the peripheral blood for a period corresponding
roughly to the first part of the erythrocytic life cycle (ring stage).
Later, in blood-stage development, parasite-encoded adhesion molecules
are inserted into the erythrocyte membrane, preventing the circulation
of the PEs. The principal molecule mediating PE adhesion is P.
falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the
polymorphic var gene family. The population of parasites is subject to
clonal antigenic variation through changes in var expression, and a
single PfEMP1 variant is expressed at the PE surface in a mutually
exclusive manner. In addition to its role in immune evasion, switches
in PfEMP1 expression may be associated with fundamental changes in
parasite tissue tropism in malaria patients. A switch from CD36
binding to chondroitin sulphate A (CSA) binding may lead to extensive
sequestration of PEs in placenta syncytiotrophoblasts. This is
probably a key event in malaria pathogenesis during pregnancy. The
CSA-binding phenotype of mature PEs is linked to another distinct
adhesive phenotype: the recently described CSA-independent
cytoadhesion of ring-stage PEs. Thus, a subpopulation of PEs that
sequentially displays these two different phenotypes may bind to an
individual endothelial cell or syncytiotrophoblast throughout the
asexual blood-stage cycle. This suggests that non-circulating
(cryptic) parasite subpopulations are present in malaria patients.
J Indian Med Assoc 2000 Oct;98(10):615-6, 618
Review of trends of malaria in an urban community of Calcutta
- Chattopadhyay O, Sengupta G
All India Institute of Hygiene and Public Health, Calcutta.
The trends in the malaria situation over the last 14 years in an urban
community of Calcutta with a population of 1,04,000 have been analysed
with particular reference to the malaria epidemic which took place in
Calcutta in November-December, 1995. Annual and monthwise data on
malariometric indices pertaining to 1984-1997 were collected from
health centre records. The total number of blood slides examined every
year has steadily increased from around 8,000 in 1984 to more than
23,000 in 1996 with some decline in 1997. About 95% of the confirmed
malaria cases were of the benign tertian type, while remaining 5% were
of the malignant tertian type. The slide vivax rate has steadily
declined over the years 1984-1997 from around 50 per cent in 1984 to
between 20 to 30 per cent during 1993-1997. The slide falciparum rate
over the same period varied between 0.5 to 2 per cent and did not show
any clear secular trend. The annual parasite incidence (API) which
varied cyclically between 40 to 60 per thousand during 1984-87
increased (with a cyclical trend superimposed on a secular increasing
trend) to vary between 50 to 70 per thousand during 1994-97. The 1995
winter epidemic of malaria was characterised by an increased
occurrence of both P vivax and P falcipanrum malaria.
Med Trop (Mars)
[No title available].
[Article in French]
Nahum A, Akogbeto M
Centre de Recherche Entomologique de Cotonou, 06 BP 2604 Cotonou,
Republique du Benin.
The purpose of this study was to evaluate the state of knowledge and
use of drug in pregnant women diagnosed with malaria at the first
prenatal examination. Survey data were conducted of physicians and
paramedical staff working the public and private sector in Cotonou,
Benin from November 1996 to January 1997. A questionnaire including
items on the type of antimalarials used, therapeutic regimens and
compliance with the treatment posology and duration guidelines as
defined by the WHO and recommended by the National Program against
Malaria. A study of informational supports allowed validation of
responses obtained during the interview on the day of survey. A random
two-degree, stratified sample of 208 prescribers including 109
physicians, 51 midwives, and 48 nurses was interviewed. Data analysis
showed that chemoprophylaxis was prescribed by all midwives, 87.5 p.
100 of nurses, and 8.2 p. 100 of physicians. Midwives prescribed this
strategy in all pregnant women. For 5.5 p. 100 of physicians and 6.3
p. 100 of nurses, primigravid women were considered as a target group.
Chloroquine was the most widely used antimalarial. It was sometimes
used in association with proguanil. Of the other drugs used for
prevention, quinine was prescribed by 2.4 p. 100 of nurses and 1.1 p.
100 of physicians. The therapeutic regimes and posologies used by the
health care workers were not in compliance with the policies of the
National Program for Control of Malaria. The findings warrant the
creation of an organization to promote consultation and communication
between health care authorities and workers.
Med Trop (Mars) 2000;60(3):243-9
[No title available].
[Article in French]
Randrianarivelojosia M, Raharimalala L, Randriamanantena A, Jambou
Laboratoire du Paludisme, l'Institut Pasteur de Madagascar,
Chloroquine is still the drug of choice for first-line treatment of
uncomplicated malaria in Madagascar. However development and spread of
chloroquine-resistance could compromise this therapeutic strategy in
the future. The purpose of this 1997 study was to compare the efficacy
of combined treatment using sulfadoxine and pyrimethamine and
single-agent treatment using chloroquine for management of
uncomplicated malaria. Study data were collected at four sites in
coastal areas of Madagascar where transmission of malaria is
perennial. Prevalence of malaria ranged from 15 p. 100 to 22 p. 100 in
school children and from 24 p. 100 to 72 p. 100 in outpatient
consulting spontaneously at community health centers. All four
Plasmodium species affecting man were identified. Plasmodium
falciparum was involved in 83 p. 100 of cases. In vivo testing of the
susceptibility of Plasmodium falciparum to chloroquine was performed
in 149 patients according to the standard simplified 7-day protocol of
the WHO. The 35 tests in school children demonstrated no evidence of
resistance. However type R1 + R2 resistance was noted in 17 of the 114
tests performed on outpatients, i.e. 14.9 p. 100. In vitro testing
demonstrated chloroquine resistance in four of the 90 specimens
tested, i.e. 4.4 p. 100. With regard to combined sulfadoxine/pyrimethamine
treatment, 45 of 46 in vivo tests in outpatients showed no evidence of
resistance. Combination treatment was more effective than single-agent
treatment (p = 0.02) and could offer an effective alternative for
Vaccine 2001 Mar 21;19(17-19):2315-8
Genomic tools for gene and protein discovery in malaria: toward new
- Carucci DJ
Malaria Program, Naval Medical Research Center, 20910, Silver Spring,
Advances in malaria vaccine and drug development have been hindered in
part by the complex multistage life cycle of the parasite, much of
which is inaccessible to study, and by a large genome encoding over
5000 genes. Two human models of immunity to malaria, however, suggest
that the development of an effective vaccine is within reach. We have
outlined a strategy to identify the expression of hundreds to
thousands of potential vaccine targets employing recently developed
technologies for gene and protein expression. Combined with the
exciting developments of malaria DNA vaccine technologies, these
approaches form the basis for malaria subunit vaccines that may mimic
the protective efficacy of our human model systems and provide the
foundation for novel approaches to vaccine development for a range of
Vaccine 2001 Mar 21;19(17-19):2309-14
Transmission blocking malaria vaccines.
- Carter R
University of Edinburgh, Division of Biological Sciences, West Mains
Road, EH9 3JT, Edinburgh, UK
Transmission blocking vaccines (TBVs) against malaria are intended to
induce immunity against the stages of the parasites which infect
mosquitoes so that TBV-immunised individuals cannot transmit malaria.
As malarial infections are transmitted mainly within a few hundreds of
meters from an infectious human source, TBVs used within in a
community would protect the immediate neighbourhood of the vaccinated
individuals. TBVs against the two major species of human malaria,
Plasmodium falciparum and P. vivax, are under development. Candidate
TBV constructs for both Plasmodium species have been successfully
tested in animal systems and testing is in progress with clinical
grade material in humans.