Library Malaria Bulletin: June 18-July 5, 2001
Sciences and Malaria
Cad Saude Publica 2001;17 Suppl:103-13
- An integrated malaria control program with
community participation on the Pacific Coast of Colombia.
Rojas W, Botero S, Garcia HI.
Corporacion para Investigaciones Biologicas, Medellin, Colombia.
- [email protected]
The study focuses on integrated malaria control in 23 communities on
the Pacific Coast of Colombia, with several elements of an ecosystem
approach to human health, including malaria-related sociopolitical,
ecological, and economic factors. The program fostered community
participation. The program presented here had 2 components:
implementation and research. The first was conducted in 23
communities, 21 of which lacked adequate health services in terms of
education, community participation, prompt diagnosis and complete
treatment, and vector control. Research focused on specific vector
control measures and the current national health services
decentralization process. The project: 1) created a malaria
prevention culture in the community; 2) avoided deaths from malaria
(no fatal cases in the 3-year period, compared to 5-8 deaths a year
previously); 3) avoided cases of cerebral malaria (no cases, as
compared to 90-110 per year previously); 4) reduced malaria
incidence by 45.36%; 5) decreased length of sick leave from 7.52 to
3.7 days; 6) established a permanent network of microscope
technicians and 2-way radio communications; 7) integrated work by
local, regional, and outside institutions; 8) demonstrated efficacy
of insecticide-impregnated bednets to reduce malaria transmission.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):85-96
- The economic burden of malaria.
Gallup JL, Sachs JD.
Center for International Development, Harvard University, Cambridge,
Massachusetts 02138, USA.
- [email protected]
Malaria and poverty are intimately connected. Controlling for
factors such as tropical location, colonial history, and
geographical isolation, countries with intensive malaria had income
levels in 1995 of only 33% that of countries without malaria,
whether or not the countries were in Africa. The high levels of
malaria in poor countries are not mainly a consequence of poverty.
Malaria is geographically specific. The ecological conditions that
support the more efficient malaria mosquito vectors primarily
determine the distribution and intensity of the disease. Intensive
efforts to eliminate malaria in the most severely affected tropical
countries have been largely ineffective. Countries that have
eliminated malaria in the past half century have all been either
subtropical or islands. These countries' economic growth in the 5
years after eliminating malaria has usually been substantially
higher than growth in the neighboring countries. Cross-country
regressions for the 1965-1990 period confirm the relationship
between malaria and economic growth. Taking into account initial
poverty, economic policy, tropical location, and life expectancy,
among other factors, countries with intensive malaria grew 1.3% less
per person per year, and a 10% reduction in malaria was associated
with 0.3% higher growth. Controlling for many other tropical
diseases does not change the correlation of malaria with economic
growth, and these diseases are not themselves significantly
negatively correlated with economic growth. A second independent
measure of malaria has a slightly higher correlation with economic
growth in the 1980-1996 period. We speculate about the mechanisms
that could cause malaria to have such a large impact on the economy,
such as foreign investment and economic networks within the country.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):68-75
- Impact of Plasmodium falciparum malaria on
performance and learning: review of the evidence.
Holding PA, Snow RW.
Centre for Geographic Medicine Research (Coast), Kenya Medical
Research Institute, Kilifi.
Despite the growing recognition that Plasmodium falciparum malaria
constitutes a major threat to child survival, the indirect
consequences of disease and infection on general human development
have been less well described. This review suggests that malaria in
childhood is likely to have effects on general cognitive and
behavioral development, which range from subtle to profound.
Nevertheless, our understanding of the numbers of affected children,
and the persistence of and recovery from impairment remains ill
defined. Only through large long-term studies will we be able to
establish the wider consequences of malaria on communities in areas
of the world where malaria is endemic.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):45-56
- The cost-effectiveness of antenatal malaria
prevention in sub-Saharan Africa.
Goodman CA, Coleman PG, Mills AJ.
Department of Public Health and Policy, London School of Hygiene and
Tropical Medicine, United Kingdom.
- [email protected]
Antimalarial chemoprophylaxis during pregnancy significantly
increases the birth weight of babies born to primigravidae, but
coverage in sub-Saharan Africa is very limited. This analysis
assessed whether increasing coverage is justified on
cost-effectiveness grounds. A standardized modeling framework was
used to estimate ranges for the cost per discounted year of life
lost averted by weekly chloroquine chemoprophylaxis and intermittent
sulfadoxine-pyrimethamine (SP) treatment for primigravidae in an
operational setting with moderate to high malaria transmission. The
SP regimen was found to be more cost-effective than the chloroquine
regimen, because of both lower costs and higher compliance. Both
regimens appear to be a good value for money in comparison with
other methods of malaria control and based on rough
cost-effectiveness guidelines for low-income countries, even with
high levels of drug resistance. However, extending the SP regimen to
all gravidae and increasing the number of doses per pregnancy could
make the intervention significantly less cost-effective.
Trop Med Int Health 2001 Jun;6(6):442-8
Community perceptions of a mass administration of
an antimalarial drug combination in The Gambia.
De Martin S, Von Seidlein L, Deen JL, Pinder M, Walraven G,
London School of Hygiene and Tropical Medicine, London, UK; Medical
Research Council Laboratories, Farafenni Field Station, Fajara, The
To test the hypothesis that widespread treatment with artemisinin
derivatives can reduce malaria transmission, a mass drug
administration (MDA) campaign was undertaken in an area of The
Gambia in 1999. Coverage of 85% of the target population was
achieved, but the intervention did not reduce overall malaria
transmission. We studied the perceptions, knowledge and attitudes of
the community to the MDA campaign. A validated questionnaire was
administered to randomly selected MDA participants (n=90) and MDA
refusers (n=71). Individuals who believed in the importance of the
MDA (adjusted OR 58.3%; 95% CI 17.4-195.8) and those who were aware
that a high level of participation was needed for the MDA to be
successful (adjusted OR 28.1; 95% CI 10.3-75.9) were more likely to
participate. Understanding that the purpose of the MDA was to reduce
malaria (adjusted OR 13.9; 95% CI 5.5-35.1) and knowledge of the
fact that malaria is transmitted by mosquitoes and of the clinical
signs of malaria (adjusted OR 3.4; 95% CI 3.1-9.0) were associated
with participation. Individuals who discussed the MDA with other
villagers (adjusted OR 5.5; 95% CI 2.2-13.5) and those who attended
the sensitization meeting (adjusted OR 2.6; 95% CI 1.1-6.0) were
also more likely to participate. Women were significantly more
likely to participate in the MDA than men (adjusted OR 3.1; 95% CI
1.5-6.2). Individuals who refused to participate were unlikely to
plan participation in future MDAs. One of the most difficult
challenges in the implementation of a malaria control strategy such
as an MDA is to convince villagers to participate and to make them
aware that a high level of participation by the community is needed
for success. We found that our sensitization meetings could be
improved by giving more information on how the MDA works and finding
means to generate small group discussions after the meeting.
Lancet 2001 Apr 21;357(9264):1241-7
- Lancet. 2001 Apr 21;357(9264):1219-20
- Lancet. 2001 Apr 21;357(9264):1284-6
Effect of large-scale social marketing of
insecticide-treated nets on child survival in rural Tanzania.
Schellenberg JR, Abdulla S, Nathan R, Mukasa O, Marchant TJ,
Kikumbih N, Mushi AK, Mponda H, Minja H, Mshinda H, Tanner M,
Ifakara Health Research and Development Centre, PO Box 53, Ifakara,
BACKGROUND: Insecticide-treated nets have proven efficacy as a
malaria-control tool in Africa. However, the transition from
efficacy to effectiveness cannot be taken for granted. We assessed
coverage and the effect on child survival of a large-scale social
marketing programme for insecticide-treated nets in two rural
districts of southern Tanzania with high perennial malaria
transmission. METHODS: Socially marketed insecticide-treated nets
were introduced step-wise over a 2-year period from May, 1997, in a
population of 480000 people. Cross-sectional coverage surveys were
done at baseline and after 1, 2, and 3 years. A demographic
surveillance system (DSS) was set up in an area of 60000 people to
record population, births, and deaths. Within the DSS area, the
effect of insecticide-treated nets on child survival was assessed by
a case-control approach. Cases were deaths in children aged between
1 month and 4 years. Four controls for each case were chosen from
the DSS database. Use of insecticide-treated nets and potential
confounding factors were assessed by questionnaire. Individual
effectiveness estimates from the case-control study were combined
with coverage to estimate community effectiveness. FINDINGS:
Insecticide-treated net coverage of infants in the DSS area rose
from less than 10% at baseline to more than 50% 3 years later.
Insecticide-treated nets were associated with a 27% increase in
survival in children aged 1 month to 4 years (95% CI 3-45). Coverage
in such children was higher in areas with longer access to the
programme. The modest average coverage achieved by 1999 in the two
districts (18% in children younger than 5 years) suggests that
insecticide-treated nets prevented 1 in 20 child deaths at that
time. INTERPRETATION: Social marketing of insecticide-treated nets
has great potential for effective malaria control in rural African
Lancet 2001 Jun 9;357(9271):1837-41
Control of malaria in Pakistan by applying
deltamethrin insecticide to cattle: a community-randomised trial.
Rowland M, Durrani N, Kenward M, Mohammed N, Urahman H, Hewitt S.
HealthNet International, University Town, Peshawar, Pakistan
Background The standard method of malaria control in south Asia,
indoor spraying of houses with residual insecticide, is becoming
prohibitively expensive to implement and new approaches are needed.
Since the region's vector mosquitoes feed predominantly on domestic
animals and only secondarily on human beings, to apply insecticide
to surfaces of cattle instead might be more costeffective. We aimed
to investigate whether domestic livestock treated with deltamethrin
(applied by a sponging method) would prove toxic to mosquitoes and
therefore aid in malaria control.Methods Six Afghan refugee
settlements in Pakistan were randomly assigned to one of two groups.
In one group livestock were treated with deltamethrin during the
malaria transmission seasons of 1995 and 1997, whereas in the other
group livestock were treated during the 1996 season. Malaria was
monitored by passive case detection at village clinics and by
cross-sectional surveillance. Mosquitoes were also
monitored.Findings According to clinic records the incidence of
malaria caused by Plasmodium falciparum decreased by 56% (95% CI
14-78%) and P vivax by 31% (5-50%) in livestock-treated villages.
Cross-sectional surveys showed comparable decreases in parasite
prevalence. The density and life expectancy of Anopheles stephensi
and A culicifacies populations were reduced in treated villages. The
efficacy of livestock treatment was similar to that of indoor
spraying but campaign costs were 80% less. When applied in a highly
endemic settlement, the incidence of falciparum malaria decreased
from 280 episodes per 1000 person-years to nine episodes per 1000
person-years.Interpretations Insecticide treatment of livestock is a
cost-effective and promising alternative for south Asia and other
regions where primary vectors are zoophilic.
Clin Infect Dis 2001 Aug 1;33(3):381-385
- Malaria Chemoprophylaxis in the Age of Drug
Resistance. II. Drugs That May Be Available in the Future.
Shanks GD, Kain KC, Keystone JS.
US Army Medical Component of the Armed Forces Research Institute of
Medical Sciences, Bangkok, Thailand.
- [email protected]
All current regimens of malaria chemoprophylaxis have serious
drawbacks as a result of either suboptimal efficacy, difficulty with
medication compliance, or adverse events. Two 8-aminoquinolines may
be approaching registration, with primaquine having completed its
prophylactic field testing and tafenoquine having begun advanced
field testing at the end of 2000. Primaquine has long been used for
management of relapses of malaria, but in the past decade, it has
been reexamined for use in malaria prevention in order to stop
infection in the liver. In field trials performed in Indonesia and
Colombia, the efficacy of primaquine for malaria prevention was
approximately 90%, compared with that of placebo. Because of its
short half-life, primaquine requires daily administration. For
adults, the prevention regimen is 30 mg base daily (0.5 mg
base/kg/day), and it can probably be discontinued soon after
departure from an area where malaria is endemic. To kill parasites
that already exist in the liver, terminal prophylaxis is given after
exposure to relapses of malaria infection; for adults, such
prophylaxis usually consists of 15 mg base (0.3 mg base/kg/day)
given daily for 2 weeks. Primaquine-induced gastrointestinal
disturbances can be minimized if the drug is taken with food.
Neither primaquine nor tafenoquine should be given to persons with
glucose-6-phosphate dehydrogenase deficiency, to avoid the
development of potentially severe drug-induced hemolysis.
Tafenoquine is an analogue of primaquine that is more potent than
the parent drug. Field trials in Kenya, Ghana, Gabon, and Southeast
Asia have demonstrated an efficacy rate of approximately 90% for
tafenoquine. Its long half-life allows for infrequent dosing
(currently tested at 200 mg base/week), and its effect on parasites
at the liver stage may allow for drug discontinuation at the time of
departure from the area of endemicity.
Gene Ther 2001 Jul;8(13):1011-23
- Safety of a GM-CSF adjuvant-plasmid DNA malaria
Parker SE, Monteith D, Horton H, Hof R, Hernandez P, Vilalta A,
Hartikka J, Hobart P, Bentley CE, Chang A, Hedstrom R, Rogers WO,
Kumar S, Hoffman SL, Norman JA.
Vical Inc., San Diego, CA, USA.
MuStDO 5 is a multivalent plasmid DNA vaccine for malaria comprised
of five plasmid DNAs encoding five proteins from Plasmodium
falciparum and one plasmid DNA encoding human GM-CSF. To evaluate
the safety of MuStDO 5, a series of pre-clinical studies were
conducted in mice and rabbits. In pharmacology studies in mice, GM-CSF
could not be detected in the serum following either intramuscular or
a combined intramuscular/intradermal administration of the vaccine,
but was readily detected in the muscle following intramuscular
administration. In a tissue distribution study in mice, MuStDO 5
plasmid DNA was detected by PCR initially in highly vascularized
tissues, while at later time-points the plasmid DNA was detected
primarily at the site(s) of injection. In GLP safety studies in mice
and rabbits, repeated intramuscular/intradermal administration of
the MuStDO 5 vaccine was found to be safe and well tolerated without
any evidence of autoimmune pathology.
Blood 2001 Jul 15;98(2):450-457
- A comparison of the in vivo kinetics of
Plasmodium falciparum ring-infected erythrocyte surface
antigen-positive and -negative erythrocytes.
Newton PN, Chotivanich K, Chierakul W, Ruangveerayuth R,
Teerapong P, Silamut K, Looareesuwan S, White NJ.
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
the Centre for Tropical Medicine, Nuffield Department of Clinical
Medicine, John Radcliffe Hospital, Oxford, United Kingdom; the
Department of Medicine, Mae Sot Hospital, Tak Province, Thailand;
and the Department of Pharmacology, Faculty of Pharmacy, Mahidol
University, Bangkok, Thailand.
Ring-infected erythrocyte surface antigen (RESA)-positive,
Plasmodium falciparum-negative red blood cells (RBCs) are cells from
which the malaria parasite has been removed by the host without the
destruction of the erythrocyte ("pitting"). The survival
of RESA-RBCs in vivo was assessed in 14 severe and 6 uncomplicated
falciparum malaria patients. The mean RESA-RBC life of 183 hours
(95% confidence interval [CI], 136-246) was longer than the median
parasite clearance time of 66 hours (range, 30-108 hours) but
shorter than the mean red cell life of 1027 hours (95% CI, 840-1213)
(P =.0004), with a median ratio of 0.2:1.0 (range, 0.1-0.7). The
estimated median percentage of parasites pitted/body transit was
0.003% (range, 0.001%-0.05%). The rate of rise of the RESA-RBC count
during the first 24 hours after antimalarial treatment was
significantly faster (P =.036) and the subsequent RESA-RBC survival
significantly shorter (P =.017) after treatment with an artemisinin
derivative than after treatment with quinine. Parasitization of red
cells leads to changes in the erythrocyte that shorten their
survival even if the parasite is removed subsequently. (Blood.
Med Vet Entomol 2001 Jun;15(2):225-30
- Dipsticks for rapid detection of plasmodium in
vectoring anopheles mosquitoes.
Ryan JR, Dav K, Emmerich E, Garcia L, Yi L, Coleman RE,
Sattabongkot J, Dunton RF, Chan AS, Wirtz RA.
Department of Entomology, Walter Reed Army Institute of Research,
Silver Spring, Maryland 20910-7500, USA.
- [email protected]
Malaria remains the most serious vector-borne disease, affecting
some 300-500 million people annually, transmitted by many species of
Anopheles mosquitoes (Diptera: Culicidae). Monoclonal antibodies
developed against specific circumsporozoite (CS) proteins of the
main malaria parasites Plasmodium falciparum and P. vivax have been
used previously for enzyme-linked immunosorbent assays (ELISA),
widely employed for detection of malaria sporozoites in vector
Anopheles for local risk assessment, epidemiological studies and
targeting vector control. However, ELISA procedures are relatively
slow and impractical for field use. To circumvent this, we developed
rapid wicking assays that identify the presence or absence of
specific peptide epitopes of CS protein of the most important P.
falciparum and two strains (variants 210 and 247) of the more
widespread P. vivax. The resulting assay is a rapid, one-step
procedure using a 'dipstick' wicking test strip. In laboratory
assessment, dipsticks identified 1 ng/ mL of any of these three CS
protein antigens, with sensitivity nearly equal to the CS standard
ELISA. We have developed and are evaluating a combined panel assay
that will be both qualitative and quantitative. This quick and easy
dipstick test (VecTest Malaria) offers practical advantages for
field workers needing to make rapid surveys of malaria vectors.
Med Vet Entomol 2001 Jun;15(2):121-5
- Current usage of nomenclature for parasitic
diseases, with special reference to those involving arthropods.
Liverpool School of Tropical Medicine, UK.
- [email protected]
Terminological confusion has been aggravated by efforts to develop a
standardized nomenclature for parasitic diseases (SNOPAD) arising
from the proposal by Kassai et al., 1988) for a standardized
nomenclature of animal diseases (SNOAPAD). To restabilize
international nomenclature of parasitic diseases it is recommended
that, whenever appropriate, names should follow the 'International
Nomenclature of Diseases' (IND) compiled by the Council for
International Organizations for Medical Sciences (CIOMS/WHO, 1987).
For diseases not included in IND, familiarity should guide the
choice of name: traditional English language names of diseases
should be preferred, e.g. 'malaria', 'scabies' or, for parasitic
diseases having no traditional name, the taxonomic name of the
causative organism should be applied, e.g. 'Brugia timori
microfilaraemia'; 'Plasmodium malariae infection'; 'Simulium
allergy'--instead of the generic derivatives proposed by SNOPAD,
i.e. brugiosis, plasmodiosis and simuliidosis, respectively. For
names of new diseases or those rarely mentioned, the suffix -osis
would normally take precedence. Generally, the name of choice for
any disease in any language should be the vernacular term, with
commonest English usage preferred for international communication,
and publications should include synonyms in the list of keywords.
BMJ 2001 Jun 30;322(7302):1567 ( Free full-text article at: http://www.bmj.com
- Effect of zinc supplementation on malaria and
other causes of morbidity in west African children: randomised
double blind placebo controlled trial.
Muller O, Becher H, van Zweeden AB, Ye Y, Diallo DA, Konate AT,
Gbangou A, Kouyate B, Garenne M.
Department of Tropical Hygiene and Public Health, Ruprecht Karls
University, 69120 Heidelberg, INF 324, Germany.
Objective: To study the effects of zinc supplementation on malaria
and other causes of morbidity in young children living in an area
holoendemic for malaria in west Africa. Design: Randomised, double
blind, placebo controlled efficacy trial. Setting: 18 villages in
rural northwestern Burkina Faso. Participants: 709 children were
enrolled; 685 completed the trial. Intervention: Supplementation
with zinc (12.5 mg zinc sulphate) or placebo daily for six days a
week for six months. Main outcome measures: The primary outcome was
the incidence of symptomatic falciparum malaria. Secondary outcomes
were the severity of malaria episodes, prevalence of malaria
parasite, mean parasite densities, mean packed cell volume,
prevalence of other morbidity, and all cause mortality. Results: The
mean number of malaria episodes per child (defined as a temperature
>/=37.5 degrees C with >/=5000 parasites/&mgr;l) was 1.7,
99.7% due to infection with Plasmodium falciparum. No difference was
found between the zinc and placebo groups in the incidence of
falciparum malaria (relative risk 0.98, 95% confidence interval 0.86
to 1.11), mean temperature, and mean parasite densities during
malaria episodes, nor in malaria parasite rates, mean parasite
densities, and mean packed cell volume during cross sectional
surveys. Zinc supplementation was significantly associated with a
reduced prevalence of diarrhoea (0.87, 0.79 to 0.95). All cause
mortality was non-significantly lower in children given zinc
compared with those given placebo (5 v 12, P=0.1). Conclusions: Zinc
supplementation has no effect on morbidity from falciparum malaria
in children in rural west Africa, but it does reduce morbidity
associated with diarrhoea.
Int J Parasitol 2001 Aug;31(10):1107-13
Complete nucleotide sequence of the 6 kb element
and conserved cytochrome b gene sequences among Indian isolates of
Sharma I, Rawat DS, Pasha ST, Biswas S, Sharma YD.
Department of Biotechnology, All India Institute of Medical
Sciences, Ansari Nagar, - 110029, New Delhi, India
The malaria parasite contains a nuclear genome with 14 chromosomes
and two extrachromosomal DNA molecules of 6 kb and 35 kb in size.
The smallest genome, known as the 6 kb element or mitochondrial DNA,
has been sequenced from several Plasmodium falciparum isolates
because this is a potential drug target. Here we describe the
complete nucleotide sequence of this element from an Indian isolate
of P. falciparum. It is 5967 bp in size and shows 99.6% homology
with the 6 kb element of other isolates. The element contains three
open reading frames for mitochondrial proteins-cytochrome oxidase
subunit I (CoI), subunit III (CoIII) and cytochrome b (Cyb) which
were found to be expressed during blood stages of the parasite. We
have also sequenced the entire cyb gene from several Indian isolates
of P. falciparum. The rate of mutation in this gene was very low
since 12 of 14 isolates showed the identical sequence. Only one
isolate showed a maximum change in five amino acids whereas the
other isolate showed only one amino acid change. However, none of
the Indian isolates showed any change in those amino acids of cyb
which are associated with resistance to various drugs as these drugs
are not yet commonly used in India.
J Parasitol 2001 Jun;87(3):626-37
Plasmodium malariae blood-stage dynamics.
McKenzie FE, Jeffery GM, Collins WE.
Department of Organismic and Evolutionary Biology, Harvard
University, Cambridge, Massachusetts 02138, USA.
We examine the dynamics of parasitemia, fever, and gametocytemia
reflected in the preintervention charts of 180 malaria-naive U.S.
neurosyphilis patients infected with the USPHS strain of Plasmodium
malariae, for malariatherapy, focusing on the 84 charts for which
more than 35 days of patency preceded intervention and daily records
encompassed 92% or more of the duration of each infection. Inoculum
size did not influence any outcome variable. Fevers (days with
temperatures > or =101 F) followed patterns that fit recognized
brood structures more often than did our approximations of merogony
cycles (via local peaks in parasitemia), but neither closely fit
textbook quartan patterns. There were no discernable patterns in
gametocytemia. Successful transmission to mosquitoes increased
following subcurative drug treatment but did not depend on
Cad Saude Publica 2001;17 Suppl:171-9
- An ecosystem approach to malaria control in an
Health Division, FES Foundation, Cali, Colombia.
We conducted a research project aimed at strengthening local
government and the community for a sustainable malaria control
strategy. The project began with a baseline diagnosis of malaria
prevalence, a KAP survey, entomology, and health services delivery,
after which an epidemiological study was performed to identify risk
factors associated with malaria, thereafter used to plan
intervention measures. A program evaluation was conducted five years
later. By using an ecosystem approach to reanalyze data, this paper
discusses how malaria arises from a complex interaction of cultural,
economic, ecological, social, and individual factors. Intervention
measures require an intersectorial and transdisciplinary approach
that does not exist at the moment. Health sector leadership is
limited, and there is no true community participation. Implications
for research, including the use of qualitative and quantitative
methods, study design, and complexity of data analysis are
discussed. Finally, implications for malaria control are discussed,
stressing the differences between the ecosystem and integrated
disease control approaches.
Lancet 2001 Jun 16;357(9272):1948-50
Fake artesunate in southeast Asia.
Newton P, Proux S, Green M, Smithuis F, Rozendaal J, Prakongpan
S, Chotivanich K, Mayxay M, Looareesuwan S, Farrar J, Nosten F,
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Artesunate is a key antimalarial drug in the treatment of multidrug-resistant
Plasmodium falciparum malaria in southeast Asia. We investigated the
distribution of counterfeit artesunate tablets by use of the
validated, simple, and inexpensive Fast Red TR dye technique. We
also aimed to identify distinguishing characteristics of the fake
drugs. Of 104 shop-bought "artesunate" samples from
Cambodia, Laos, Myanmar (Burma), Thailand, and Vietnam, 38% did not
contain artesunate. Characteristics such as cost and physical
appearance of the tablets and packaging reliably predicted
authenticity. The illicit trade in counterfeit antimalarials is a
great threat to the lives of patients with malaria. The dye test
will assist national malaria control authorities in urgently needed
campaigns to stop this murderous trade.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):97-106
- The neglected burden of Plasmodium vivax
Mendis K, Sina BJ, Marchesini P, Carter R.
Roll Back Malaria, World Health Organization, Geneva, Switzerland. [email protected]
We estimate that the global burden of malaria due to Plasmodium
vivax is approximately 70-80 million cases annually. Probably
approximately 10-20% of the world's cases of P. vivax infection
occur in Africa, south of the Sahara. In eastern and southern
Africa, P. vivax represents around 10% of malaria cases but < 1%
of cases in western and central Africa. Outside of African, P. vivax
accounts for > 50% of all malaria cases. About 80-90% of P. vivax
outside of Africa occurs in the Middle East, Asia, and the Western
Pacific, mainly in the most tropical regions, and 10-15% in Central
and South America. Because malaria transmission rates are low in
most regions where P. vivax is prevalent, the human populations
affected achieve little immunity to this parasite; as a result, in
these regions, P. vivax infections affect people of all ages.
Although the effects of repeated attacks of P. vivax through
childhood and adult life are only rarely directly lethal, they can
have major deleterious effects on personal well-being, growth, and
development, and on the economic performance at the individual,
family, community, and national levels. Features of the transmission
biology of P. vivax give this species greater resilience than the
less robust Plasmodiumfalciparum in the face of conditions adverse
to the transmission of the parasites. Therefore, as control measures
become more effective, the residual malaria burden is likely
increasingly to become that of P. vivax.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):76-84
- Toward a framework and indicators for
monitoring Roll Back Malaria.
Remme JHE, Binka E, Nabarro D.
United Nations Development Programme/World Bank/World Health
Organization Special Programme for Research and Training in Tropical
Diseases, World Health Organization, Geneva, Switzerland.
- [email protected]
Roll Back Malaria (RBM) is a new global partnership that aims to
halve the malaria burden by the year 2010. A framework and
indicators for monitoring the outcomes and impact of RBM have been
defined through an extensive consultative process. The framework
identifies critical areas for monitoring RBM action relating to 1)
the impact on malaria burden, 2) improvements in malaria prevention
and treatment, 3) related health sector development, and 4) support
for RBM action (including partnerships). A set of RBM indicators has
been defined that corresponds to these critical areas but that
reflects the major variations in malaria epidemiology and the
principal interventions in different parts of the world. Countries
would select indicators that are appropriate for their situation.
Four global indicators are proposed for use by all countries in
which RBM action is under way. Data collection procedures are
discussed, and it is indicated how monitoring RBM action can build
on existing data-collection mechanisms.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):57-67
- Gaps in the childhood malaria burden in Africa:
cerebral mialaria, neurological sequelae, anemia, respiratory
distress, hypoglycemia, and complications of pregnancy.
Murphy SC, Breman JG.
Department of Veterinary Microbiology and Preventive Medicine, Iowa
State University, Ames, USA.
Evaluations of the African childhood malaria burden do not fully
quantify the contributions of cerebral malaria (CM), CM-associated
neurological sequelae, malarial anemia, respiratory distress,
hypoglycemia, and pregnancy-related complications. We estimated the
impact of these malaria manifestations on members of the African
population < 5 years old. Calculations were based on an extensive
literature review that used National Library of Medicine search
engines, other bibliographic sources, and demographic data. In
sub-Saharan Africa, CM annually affects 575,000 children < 5
years of age and 110,000 (approximately 19% case fatality rate [CFR])
die. Childhood survivor, of CM experience developmental and
behavioral impairments: each year, 9,000-19,000 children (> 2% of
survivors of CM) < 5 years of age in Africa experience
neurological complications lasting > 6 months. Severe malarial
anemia heavily burdens hospitals with rising admission and CFRs and
with treatments that are complicated by limited and sometimes
contaminated blood supplies. Severe malarial anemia occurs 1.42-5.66
million times annually and kills 190,000-974,000 (> 13% CFR)
children < 5 years of age annually. Respiratory distress,
hypoglycemia, and overlapping clinical manifestations cause
1.12-1.99 million cases and > 225,000 (> 18% CFR) additional
deaths among African children with malaria. Maternal, placental, or
fetal malaria infection during pregnancy adversely affects
development and survival of fetuses and newborns through low birth
weight (LBW), maternal anemia, and possibly abortion and stillbirth.
Between 167,000 and 967,000 cases of malaria-associated LBW occur
yearly; malaria-induced LBW kills 62,000-363,000 (> 38% CFR)
newborns each year. All the gaps in the burden comprise 0.4-1.7
million deaths annually, > 50% of which are due to severe
malarial anemia. These malaria-induced medical problems constitute
major clinical, public health, and research challenges in that they
may contribute to more than double the mortality than is generally
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):36-44
- The epidemiology and burden of Plasmodium
falciparum-related anemia among pregnant women in sub-Saharan
Guyatt HL, Snow RW.
Kenya Medical Research Institute/Wellcome Trust Collaborative
- [email protected]
The paucity of precise information on the burden of malaria among
pregnant women has hampered effective lobbying for the inclusion of
preventative strategies against malaria in Safe Motherhood
Initiatives. This article reviews the evidence on the coincidental
risks of malaria and anemia in Africa and attempts to estimate the
probable burden of malaria-related severe anemia in this susceptible
group. Twenty-six studies on hemoglobin levels in all-parity
pregnant women throughout this region could be matched with a
malaria parasite ratio in children < 15 yr old (a measure of the
intensity of transmission). In areas with no malaria, the mean
hemoglobin levels were markedly higher than those found in areas
with stable malaria transmission, though changes with increasing
intensity of transmission were unclear. Eighteen studies from areas
with stable malaria transmission in sub-Saharan Africa suggested
that the median prevalence of severe anemia in all-parity pregnant
women is approximately 8.2%. Assuming that 26% of these cases are
due to malaria, it is suggested that as many as 400,000 pregnant
women may have developed severe anemia as a result of infection with
malaria in sub-Saharan Africa in 1995.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):28-35
- The burden of malaria in pregnancy in
Steketee RW, Nahlen BL, Parise ME, Menendez C.
Division of Parasitic Diseases, National Center for Infectious
Diseases, Centers for Disease Control and Prevention, Public Health
Service, US Department of Health and Human Services, Atlanta,
Georgia 30333, USA.
- [email protected]
Pregnant women in malarious areas may experience a variety of
adverse consequences from malaria infection including maternal
anemia, placental accumulation of parasites, low birth weight (LBW)
from prematurity and intrauterine growth retardation (IUGR), fetal
parasite exposure and congenital infection, and infant mortality
(IM) linked to preterm-LBW and IUGR-LBW. We reviewed studies between
1985 and 2000 and summarized the malaria population attributable
risk (PAR) that accounts for both the prevalence of the risk factors
in the population and the magnitude of the associated risk for
anemia, LBW, and IM. Consequences from anemia and human
immunodeficiency virus infection in these studies were also
considered. Population attributable risks were substantial: malaria
was associated with anemia (PAR range = 3-15%), LBW (8-14%),
preterm-LBW (8-36%), IUGR-LBW (13-70%), and IM (3-8%). Human
immunodeficiency virus was associated with anemia (PAR range =
12-14%), LBW (11-38%), and direct transmission in 20-40% of
newborns, with direct mortality consequences. Maternal anemia was
associated with LBW (PAR range = 7-18%), and fetal anemia was
associated with increased IM (PAR not available). We estimate that
each year 75,000 to 200,000 infant deaths are associated with
malaria infection in pregnancy. The failure to apply known effective
antimalarial interventions through antenatal programs continues to
contribute substantially to infant deaths globally.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):18-27
- All-cause mortality among young children in
western Kenya. VI: the Asembo Bay Cohort Project.
McElroy PD, ter Kuile FO, Hightower AW, Hawley WA,
Phillips-Howard PA, Oloo AJ, Lal AA, Nahlen BL.
Division of Parasitic Diseases, National Center for Infectious
Diseases, Centers for Disease Control and Prevention, Atlanta,
Georgia 30333, USA.
- [email protected]
Although all-cause mortality has been used as an indicator of the
health status of childhood populations, such data are sparse for
most rural areas of sub-Saharan Africa, particularly community-based
estimates of infant mortality rates. The longitudinal follow-up of
more than 1,500 children enrolled at birth into the Asembo Bay
Cohort Project (ABCP) in western Kenya between 1992 and 1996 has
provided a fixed birth cohort for estimating all-cause mortality
over the first 5 yr of life. We surveyed mothers and guardians of
cohort children in early 1999 to determine survival status. A total
of 1,260 households were surveyed to determine the survival status
of 1,556 live births (99.2% of original cohort, n = 1,570). Most
mothers (66%) still resided but 27.5% had migrated, and 5.5% had
died. In early 1999, the overall cumulative incidence of all-cause
mortality for the entire 1992-1996 birth cohort was 26.5% (95%
confidence interval, 24.1-28.9%). Neonatal and infant mortality were
32 and 176 per 1,000 live births, respectively. These
community-based estimates of mortality in the ABCP area are
substantially higher than for Kenya overall (nationally, infant
mortality is 75 per 1,000 live births). The results provide a
baseline description of all-cause mortality among children in an
area with intense Plasmodium falciparum transmission and will be
useful in future efforts to monitor changes in death rates
attributable to control programs for specific diseases (e.g.,
malaria and HIV/AIDS) in Africa.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):12-7
- The public health impact of chloroquine
resistance in Africa.
Laboratoire de Paludologie, Institut de Recherche pour le
Developpement (IRD, formerly ORSTOM), Dakar, Senegal.
- [email protected]
Between 1978 and 1988 Plasmodium falciparum resistance to
chloroquine has been reported in all countries of tropical Africa.
Despite the intensification of resistance during the last 2 decades,
chloroquine remains in 2000 the first-line treatment for malaria in
most of these countries. Here we review published data on the public
health impact of antimalarial drug resistance in Africa. These data
show that since the late 1980s convincing evidence of a major public
health impact of the spread of chloroquine resistance has been
available. Hospital studies in various African countries have
documented a 2- or 3-fold increase in malaria deaths and admissions
for severe malaria, an increase temporally related to the emergence
of chloroquine resistance. Data from sentinel demographic
surveillance systems in Senegal indicated that mortality
attributable to malaria in children increased by as much as 6-fold
among populations where low levels of malaria mortality had been
achieved because of efficient health services before the emergence
of chloroquine resistance. Increasing incidence of severe malarial
anemia also contributed to human immunodeficiency virus
dissemination. The dramatic impact of chloroquine resistance on
malaria mortality has long been underestimated because only a low
proportion of malaria attacks are potentially lethal among persons
continuously exposed since birth to high levels of transmission.
There is an urgent need to change treatment policies in Africa.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):1-11
- The ears of the hippopotamus: manifestations,
determinants, and estimates of the malaria burden.
Fogarty International Center, National institutes of Health,
Bethesda, Maryland 20892-2220, USA.
- [email protected]
Malarious patients experience asymptomatic parasitemia; acute
febrile illness (with cerebral damage, anemia, respiratory distress,
hypoglycemia); chronic debilitation (anemia, malnutrition, nervous
system-related sequelae); and complications of pregnancy (anemia,
low birth weight, increased infant mortality). These manifestations
in patients, communities, and countries reflect intrinsic (human,
parasite, mosquito) and extrinsic (environmental, social,
behavioral, political, and economic conditions as well as
disease-control efforts) determinants. At a minimum, between 700,000
and 2.7 million persons die yearly from malaria, over 75% of them
African children. Between 400 and 900 million acute febrile episodes
occur yearly in African children under 5 yr of age living in endemic
areas. Although about half of these children are parasitemic, all
merit consideration of malaria-specific therapy, which is becoming
more problematic because of parasite resistance to drugs. These
numbers will more than double over the next 20 yr without effective
control. Fewer than 20% of these febrile episodes and deaths come to
the attention of any formal health system. The relatively few ill
patients who have any contact with the health services represent the
"ears of the hippopotamus." Greatly intensified research
activities and control of the intolerable burden of malaria are
mandatory if economic development is to accelerate in Africa. In
particular, support should be targeted to understanding and
preventing malaria-induced anemia, hypoglycemia, effects on
pregnancy, and neurologic and developmental impairment. To decrease
and stop transmission of this intolerable scourge, there is an
urgent need for malaria vaccines, newer drugs, and better vector
control methods as well as the ability to improve current
technologies and use them more efficiently.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):9-11
Limited polymorphism in Plasmodium falciparum
Niederwieser I, Felger I, Beck HP.
Swiss Tropical Institute, Basel.
In areas highly endemic for malaria, individuals are frequently
found to be infected simultaneously with multiple Plasmodium
falciparum clones. This raises the question of whether all parasite
clones produce gametocytes equally or whether gametocytogenesis is
suppressed in some clones. In order to assess this in
epidemiological studies, polymorphic genes specifically expressed in
gametocytes could be analyzed by both amplification of genomic DNA
from blood samples and by reverse transcribed polymerase chain
reaction amplifying expressed gametocyte-specific genes only. Here
we report the analysis of diversity in the three gametocyte-specific
genes Pfs16, Pfs48/45, and Pfs230. In addition to the previously
published data, limited polymorphism was found in the coding
sequences of Pfs16 and Pfs48/45. Larger polymorphism was identified
in Pfs230, which might allow the development of a discriminating PCR-based
genotyping scheme for transmission studies. However, the limited
polymorphism in Pfs16 and Pfs48/45 renders these molecules poorly
useful for such studies.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):6-8
Short report: increased susceptibility to
Plasmodium malariae in pregnant alpha(+)-thalassemic women.
Mockenhaupt FP, Rong B, Till H, Thompson WN, Bienzle U.
Institute of Tropical Medicine Berlin, Medical Faculty Charite,
Humboldt-University Berlin, Germany.
The influence of alpha(+)-thalassemia on malaria in pregnancy was
assessed in a cross-sectional study of 530 women in Ghana.
Plasmodial infections, alpha(+)-thalassemia, serum levels of
C-reactive protein, and antimalarial drugs in urine were determined.
The alpha-globin genotypes did not correlate with the prevalence of
Plasmodium falciparum-infection and parasite densities. However,
Plasmodium malariae tended to be more frequent in alpha(+)-thalassemic
women (P = 0.05). Excluding women with residual antimalarials, a
significant excess of P. malariae was observed in alpha(+)-thalassemic
individuals. Febrile responses (P = 0.05) and inflammation (CRP >
0.6 mg/dl, P = 0.06) appeared to be less common in infected
alpha(+)-thalassemic women and were also comparatively rare in
parasitemic individuals who harbored double species infections with
P. falciparum and P. malariae. Plasmodium malariae may influence the
pathogenesis of falciparum malaria leading to a low prevalence of
inflammation and febrile responses in alpha(+)-thalassemic women.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):58-66
Hemoglobin concentration in children in a malaria
holoendemic area is determined by cumulated Plasmodium falciparum
Ekvall H, Premji Z, Bennett S, Bjorkman A.
Unit of Infectious Diseases, Karolinska Institute, Karolinska
Hospital, Stockholm, Sweden.
- [email protected]
In malaria holoendemic areas children are anemic, but the exact
influence of falciparum malaria on hemoglobin (Hb) concentration
remains largely unsettled. Prospective data were therefore collected
in children < 24 months of age during five months in a Tanzanian
village. Children with mean asymptomatic parasitemia > or = 400/microl
had lower median Hb levels during the study than those with mean
density < 400/microl. The difference was 9.7 g/L (95% confidence
interval [CI] 2.8-17). In children with one or more clinical malaria
episodes, the median Hb was 8.3 g/L (95% CI 0.9-16) lower than those
without episode. If early treatment failure was recorded, the
immediate effect on Hb was particularly important with a mean drop
of 17 g/L. Interestingly, at study-end the Hb concentration
represented a function of the area under the parasitemia curve (AUPC)
during the previous five months, adjusting for age. In conclusion,
stepwise deterioration in median Hb levels was found by asymptomatic
parasitemia, clinical malaria episode, and most significantly,
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):32-4
Comparison of direct and membrane feeding methods
to infect Anopheles arabiensis with Plasmodium falciparum.
Awono-Ambene HP, Diawara L, Robert V.
Laboratoire de Paludologie, Institut de Recherche pour le
Developpement, Dakar, Senegal.
Two standard methods are available to infect mosquitoes with malaria
parasites: direct feeding through the skin of the gametocyte
carrier, and membrane feeding. Anopheles arabiensis collected at
larval stages and reared in an insectary were fed in parallel by
feeding on Plasmodium falciparum gametocyte carriers and by membrane
feeding on venous blood of the same gametocyte carriers. Infection
of mosquitoes was assessed at Day 7 post bloodmeal by oocyst count
of the mosquito midguts. The following parameters were not
significantly different between the two methods: the percentage of
gametocyte carriers infective for at least one mosquito (52.4%
through the skin versus 57.1% through the membrane), the mean
infection rate of mosquitoes (10.0% versus 11.3%), the geometric
mean oocyst number per mosquito (2.51 versus 3.83). In conclusion,
infection of mosquitoes by membrane feeding was similar to infection
by direct feeding. Most of the volunteers preferred venipuncture to
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):28-31
Short report: differences in dihydrofolate
reductase but not dihydropteroate synthase alleles in Plasmodium
falciparum isolates from geographically distinct areas in Malaysia.
Cox-Singh J, Zakaria R, Abdullah MS, Rahman HA, Nagappan S, Singh
Faculty of Medicine and Health Sciences, University Malaysia
Dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr)
alleles were typed in 67 Malaysian Plasmodium falciparum isolates.
The isolates were collected from two geographically distinct
locations: 51 from Sabah, Malaysian Borneo, where sulfadoxine/pyrimethamine
(SDX/PYR) is used to treat uncomplicated malaria and 16 from
Peninsular Malaysia where in vivo resistance to SDX/PYR has been
reported. A total of seven dhps alleles were identified with no
significant difference in allele frequency between the 2
populations. Two of the dhps alleles described here have not been
previously reported. Four dhfr alleles were detected in 67 P.
falciparum isolates. Eighty-seven percent of the isolates from the
Peninsula, where clinical SDX/PYR failure has been reported, had
dhfr alleles with triple point mutations while all of the isolates
from Sabah had dhfr alleles with 2 or less point mutations. The
difference in dhfr allele frequency between the two populations was
highly significant. There was no correlation between in vitro PYR
response and accumulation of dhfr point mutations.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):20-3
Diagnosis of imported malaria by Plasmodium
lactate dehydrogenase (pLDH) and histidine-rich protein 2
(PfHRP-2)-based immunocapture assays.
Iqbal J, Hira PR, Sher A, Al-Enezi AA.
Department of Microbiology, Faculty of Medicine, Kuwait University,
Safat. [email protected]
This study was conducted to evaluate the performance of two rapid
non-microscopic assays: Plasmodium lactate dehydrogenase (pLDH)
assay (OptiMAL) and Plasmodium falciparum histidine-rich protein 2
(PfHRP-2) assay (ICT Malaria). The assays were used to detect
malaria infection in 515 immigrants living in Kuwait. The
performance of both assays was compared to that of microscopy of
Giemsa-stained thick blood films and to each other. Of the 515
patients tested, 163 were positive for malaria parasites by
microscopy of thick blood film. Of these, 87 were infected with
Plasmodium vivax parasites, 63 with P. falciparum, 1 with Plasmodium
malariae, and 12 had mixed infections of P. falciparum and P. vivax.
The PfHRP-2 assay detected 53 P. falciparum infections and, as
expected, failed to detect all but one case of P. vivax. Three cases
of mixed infections were also not detected by this assay. The pLDH
assay detected 56 P. falciparum cases and 77 P. vivax infections but
failed to detect 4 cases of mixed infections. Compared to
microscopy, the performance of both the assays to diagnose P.
falciparum infection was comparable. The sensitivity for the PfHRP-2
assay was 82% with a specificity of 99.0% and for the pLDH assay the
sensitivity was 89% with a specificity of 99.5%. The PfHRP-2 assay
detected 4 false positive cases, 2 of which were also detected by
the pLDH assay. These patients reported treatment with chloroquine
in the last 2-5 weeks. Though the immunocapture diagnostic assays
may be helpful in certain situations, microscopy of thick blood film
is still the method of choice in diagnosing imported malaria.
Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):1-5
CR1 density polymorphism on erythrocytes of
falciparum malaria patients in Thailand.
Nagayasu E, Ito M, Akaki M, Nakano Y, Kimura M, Looareesuwan S,
The Institute of Science and Technology, Tokai University, Isehara,
Complement receptor type 1 (CR1) on erythrocytes shows an inherited
numerical polymorphism which correlates with a HindIII-RFLP
(restriction fragment length polymorphism) of the CR1 gene in
various populations. To investigate the relationship between CR1
density polymorphism and disease severity, we typed 185 Thai
patients with acute falciparum malaria (55 severe and 130
uncomplicated) for their genotypes of this polymorphism. The level
of expression of erythrocyte CR1 from 42 randomly selected patients
was measured by enzyme-linked immunosorbent assay (ELISA). We
observed a significantly higher frequency of homozygotes of the CR1
low density allele (LL) among the severe group as compared to the
uncomplicated group (P = 0.005). CR1 expression on erythrocytes from
patients with the LL genotype was significantly lower than
homozygotes with the high density allele (HH) (P < 0.0001) and
heterozygotes (HL) (P = 0.013). The results suggest that a
genetically-determined low CR1 density on erythrocytes may be a risk
factor for developing a more severe form of malaria in Thai
Trends Parasitol 2001 Jul;17(7):331-7
Parasite adhesion and immune evasion in placental
Beeson JG, Reeder JC, Rogerson SJ, Brown GV.
Dept of Medicine, University of Melbourne, Royal Melbourne Hospital,
VIC 3050, Parkville, Australia
Parasite sequestration in the placenta is a key feature of infection
by Plasmodium falciparum during pregnancy and is associated with
severe adverse outcomes for both mother and baby. Here, James Beeson
and colleagues draw together the findings of recent studies on
parasite mechanisms that mediate this process. They review evidence
for novel parasite variants that appear able to evade pre-existing
immunity, for the adhesion of P. falciparum-infected erythrocytes to
placental glycosaminoglycans (and the molecular basis of these
parasite properties) and for the expression of var genes encoding
the variant antigen and adhesive ligand P. falciparum-erythrocyte
membrane protein 1 (PfEMP1).
Trends Parasitol 2001 Jul;17(7):307-9
Rapid diagnostic techniques for malaria control.
Armed Forces Research Institute of Medical Sciences (AFRIMS), 315/6
Rajvithi Road, 10400, Bangkok, Thailand
The past decade was a milestone in the development of malaria
diagnostic technology. Today, a variety of simplified and rapid
malaria diagnostic devices, collectively referred to as 'dipsticks',
is available. This paper discusses the potential roles of these
devices, and obstacles to their use, in supporting malaria control
Trop Med Int Health 2001 Jun;6(6):458-62
PCR-based ELISA technique for malaria diagnosis
of specimens from Thailand.
Laoboonchai A, Kawamoto F, Thanoosingha N, Kojima S, Scott Miller
RR, Kain KC, Wongsrichanalai C.
Armed Forces Research Institute of Medical Sciences (AFRIMS),
We performed a field evaluation of polymerase chain reaction (PCR)-based
enzyme-linked immuno-sorbent assays (ELISA) for the diagnosis of
malaria. A commercially available PCR-ELISA microplate hybridization
(MPH) assay was used. Blood specimens were collected from 300
volunteers seeking care at malaria clinics in Thailand. Examination
of 200 high power fields by Giemsa-stained thick and thin smear (GTTS)
revealed 51 P. falciparum (Pf), 45 P. vivax (Pv), seven mixed Pf-Pv
infections. These plus a random sample of 48 GTTS-negative specimens
were selected for this study. All 151 specimens were processed for
parasite DNA extraction and assayed by PCR-MPH. The target DNA
sequence of the 18S small subunit ribosomal RNA (SSUrRNA) gene was
amplified by PCR and hybridized with species-specific probes for Pf,
Pv, P. malariae (Pm) and P. ovale (Po) immobilized in the wells of
the microtiter plate and detected by colorimetric assay. Colour
development was assessed at an optical density (OD) of 405 nm. An
absorbance reading of > or = 0.1 was used as a positive cut-off.
In comparison with GTTS results, PCR-MPH sensitivity was 91.4%
(53/58, 95% CI 84.2-98.6) for Pf, 94.2% (49/52, 87.9-100) for Pv and
specificity was 95.8% (46/48, 95% CI 90.2-100). There was
statistically significant positive correlation between parasite
densities < or = 7000/microl blood and absorbance reading,
suggestive of PCR-MPH being semiquantitative. PCR-MPH also detected
additional Pf and Pv cases as well as Pm and Po.
Trop Med Int Health 2001 Jun;6(6):429-34
Therapeutic efficacy of sulphadoxine/pyrimethamine
and susceptibility in vitro of P. falciparum isolates to
sulphadoxine-pyremethamine and other antimalarial drugs in Malawian
Takechi M, Matsuo M, Ziba C, MacHeso A, Butao D, Zungu IL,
Chakanika I, Bustos MD.
Community Health Sciences Unit, Ministry of Health and Population,
Malawi; Research Institute of Tropical Medicine, Ministry of Health,
Since 1993 sulphadoxine/pyrimethamine (SP) has been used as the
first-line drug for uncomplicated Plasmodium falciparum malaria in
Malawi. To investigate the current efficacy of SP and other
antimalarial drug resistance, we studied in vivo and in vitro
responses to SP, chloroquine (CQ), mefloquine (MF), quinine (QN),
and halofantrine (HF) in Salima, central Malawi. In a follow-up of
14 days, nine (13.8%) of 65 children under five showed RII/RIII
parasitological resistance, and in in vitro microtests 18 (62.1%) of
29 isolates showed <90% inhibition of schizont maturation at
pyrimethamine 75 nmol/l blood medium mixture, indicating resistance.
The discrepancy between in vivo and in vitro results might be
partially explained by acquired immunity in this holoendemic area.
In vitro one (3.4%) of 29 isolates failed schizont inhibition at 1.6
&mgr;mol/l blood of CQ, indicating resistance. Compared with an
in vitro study conducted in 1988 in another region of Malawi using
the same cut-off point, the proportion of resistant isolates had
decreased significantly (P < 0.01). Although 31% of isolates were
borderline, showing schizont maturation at 0.8 &mgr;mol/l blood
but no schizonts at 1.6 &mgr;mol/l in our study, the results
suggest possible recovery of CQ sensitivity after long-term absence
of drug pressure. Resistance remains a major problem in malaria
control. Monitoring resistance patterns in vitro provides early
warning signs of impending loss of therapeutic efficacy of the
standard treatment, and may detect changing patterns in alternative
Trop Med Int Health 2001 Jun;6(6):423-8
Diagnostic accuracy and case management of
clinical malaria in the primary health services of a rural area in
Font F, Alonso Gonzalez M, Nathan R, Kimario J, Lwilla F, Ascaso
C, Tanner M, Menendez C, Alonso PL.
Unidad de Epidemiologia y Bioestadistica, Hospital Clinic/IDIBAPS,
Universidad Barcelona, Spain; Ifakara Health Research and
Development Center, Ifakara, Tanzania; Swiss Tropical Institute,
Malaria control continues to rely on the diagnosis and prompt
treatment of both suspected and confirmed cases through the health
care structures. In south-eastern Tanzania malaria is one of the
leading causes of morbidity and mortality. The absence of
microscopic examination in most of the health facilities implies
that health workers must rely on clinical suspicion to identify the
need of treatment for malaria. Of 1558 randomly selected paediatric
consultations at peripheral health facilities throughout Kilombero
District, 41.1% were diagnosed by the attending health worker as
clinical malaria cases and 42.5% prescribed an antimalarial.
According to our malaria case definition of fever or history of
fever with asexual falciparum parasitaemia of any density, 25.5% of
all children attending the health services had malaria. This yielded
a sensitivity of 70.4% (IC95%=65.9-74.8%) and a specificity of 68.9%
(IC95%=66.2-71.5%). Accordingly, 30.4% of confirmed cases left with
no antimalarial treatment. Among malaria-diagnosed patients, 10%
were underdosed and 10.5% were overdosed. In this area, as in many
African rural areas, the low diagnostic accuracy may imply that the
burden of malaria cases may be overestimated. Greater emphasis on
the functioning and quality of basic health services in rural
endemic areas is required if improved case management of malaria is
to help roll back this scourge.
Mol Biol Evol 2001 Jul;18(7):1353-64
Evidence for Recent Population Expansion in the
Evolutionary History of the Malaria Vectors Anopheles arabiensis and
Donnelly MJ, Licht MC, Lehmann T.
Division of Parasitic Diseases, Centers for Disease Control and
Prevention, Atlanta, Georgia. Division of Parasite and Vector
Biology, Liverpool School of Tropical Medicine, Liverpool, England.
Gene flow in malaria vectors is usually estimated based on
differentiation indices (e.g., F(ST)) in order to predict the
contemporary spread of genes such as those conferring resistance to
insecticides. This approach is reliant on a number of assumptions,
the most crucial, and the one most likely to be violated in these
species, being mutation-migration-drift equilibrium. Tests of this
assumption for the African malaria vectors Anopheles gambiae and
Anopheles arabiensis are the focus of this study. We analyzed
variation at 18 microsatellite loci and the ND5 region of the
mitochondrial genome in two populations of each species. Equilibrium
was rejected by six of eight tests for the A. gambiae population
from western Kenya and by three tests in eastern Kenya. In western
Kenya, all departures from equilibrium were consistent with a recent
population expansion, but in eastern Kenya, there were traces of a
recent expansion and a bottleneck. Equilibrium was also rejected by
two of the eight tests for both A. arabiensis populations; the
departure from equilibrium was consistent with an expansion. These
multiple-locus tests detected a genomewide effect and therefore a
demographic event rather than a locus-specific effect, as would be
caused by selection. Disequilibrium due to a recent expansion in
these species implies that rates of gene flow, as inferred from
differentiation indices, are overestimates as they include a
historical component. We argue that the same effect applies to the
majority of pest species due to the correlation of their demography
with that of humans.
J Trop Pediatr 2001 Jun;47(3):165-9
Comparison of chloroquine with artesunate in the
treatment of cerebral malaria in Ghanaian children.
Goka BQ, Adabayeri V, Ofori-Adjei E, Quarshie B, Asare-Odei G,
Akanmori BD, Kurtzhals J, Ofori-Adjei D, Neequaye J.
Department of Child Health, Korle Bu Teaching Hospital, Accra,
Despite previously reported chloroquine-resistant forms of PF
falciparum in Ghana, chloroquine remains the drug of choice in
severe malaria. Artemisinin derivatives have been shown to be
effective against chloroquine-resistant strains in other endemic
areas. This open randomized study was conducted to compare the
efficacy of chloroquine and artesunate in the treatment of childhood
cerebral malaria. Out of 82 subjects that fulfilled the inclusion
criteria, 36 were randomized to receive chloroquine and 46 to
receive artemisinin. Blantyre coma scores, temperature and
parasitaemia were monitored. Mortality and neurological deficits
were documented. There was no difference in mortality rates (chloroquine,
16.7 per cent; artesunate, 21.7 per cent; p = 0.6), neurological
deficit at day 14 (chloroquine, 0 per cent; artesunate, 4.3 per
cent; p = 0.3), resolution of fever (p = 0.55), and coma recovery
time (p = 0.8), between the two groups. The results suggest that
syrup chloroquine and intramuscular/oral artesunate currently give
comparable clinical responses in the treatment of cerebral malaria
in Ghana. Possible reasons for this are discussed, and suggestions
are made for future antimalarial drug policy.