EHP Library Malaria Bulletin 55: Mar 10-23, 2003
                   Social Sciences and Malaria Control

Social science & medicine : (1982),  2002, 55 (12) 2215-2226


Strategies to improve adherence to recommended chloroquine treatment

regimes: a quasi-experiment in the context of integrated primary health

care delivery in Ghana



Guy; EVANS David


District Health Administration, P.O. Box 1, Dodowa, Ghana; Health

Research Unit, P.O. Box 184, Adabraka, Ghana; Ghana Health Service, P.O.

Box M44, Accra, Ghana; Liverpool School of Topicial Medicine, Liverpool L3

5QA, United Kingdom; World Health Organization, 1211 Geneva, Switzerland


This  paper  presents the results of an intervention study carried out as

part of the activities of a District Health Management Team responsible for

integrated  primary  health care delivery in a rural district in Ghana. The

aim  was  to  test  the  impact  of  a  combination of improved information

provision  to  patients  and  drug  labeling  on  adherence  to recommended

anti-malarial  treatment  regimens  focusing  on  oral chloroquine, for the

outpatient  management  of  acute  uncomplicated  malaria.  The study had a

quasi-experimental  pre-test  post-test  control  group  design with partly

random  allocation  by  clinic.  The  results  show  that  the intervention

resulted   in  an  improved  flow  of  information  to  clients  prescribed

chloroquine,  and  better labeling of drugs for the home treatment of acute

clinical  episodes  of  malaria  in  the intervention area. Improvements in

adherence  occurred in all clinics. However, improvements in adherence were

most  marked  in  the  clinic that was worst performing at the start of the

intervention.  Implications  of  the  results  for  improving  adherence to

chloroquine therapy on an outpatient basis are discussed.

Soc Sci Med  2003 Apr;56(8):1705-17 
Social and health determinants of the efficiency of cotton farmers
in Northern Cote d'Ivoire.
Audibert M, Mathonnat J, Henry MC.
Centre d'Etudes et de Recherches sur le Developpement International, Universite
d'Auvergne, 65 Bd. F. Mitterrand, 63000, Clermont-Ferrand, France
This article assesses the role of malaria and some social determinants on the
agricultural development and more precisely on efficiency in the context of
cotton crop in the Korhogo region in the North of Cote d'Ivoire. Data
envelopment analyses (DEA) was first applied for the purpose of calculating
relative efficiencies in production. A Tobit regression model was then used to
explain the variation in the DEA scores and check the hypotheses that the
efficiency deviations between farmers can be explained by the disparity of
malaria morbidity rate among the farmers and their family, by social
cohesiveness and cultural behaviour.Field data were collected by the authors
between March 1997 and February 1998 on 700 rural households living in three
rice production systems differently exposed to the malaria risk. Two malaria
indicators were used for the active (11-55 years old) family members of the
farm: Plasmodium falciparum infection rate and high parasite density infection
rate. The DEA model was applied on the sub-sample of cotton growers (about one
third of the households of the full sample). Results of the different DEA and
Tobit models (depending of the production process hypothesis) show that high
parasite density infection has a direct and indirect negative effect on
efficiency in the cotton crop. They also show that more cotton growers in the
village improve efficiency, although villages where cotton is growing more
widespread have weaker social cohesion. PMID: 12639587
J Ethnopharmacol  2003 Feb;84(2-3):235-239 
In vitro antiplasmodial activity of some plants used in Kisii, Kenya against
malaria and their chloroquine potentiation effects.
Muregi FW, Chhabra SC, Njagi EN, Lang'at-Thoruwa CC, Njue WM, Orago AS, Omar SA,
Ndiege IO.
Biochemistry Department, Kenyatta University, P.O. Box 43844, Nairobi, Kenya
Fifty-five organic and aqueous extracts of 11 plants used in malaria therapy in
Kisii District, Kenya were tested in vitro against chloroquine (CQ)-sensitive
and resistant strains of Plasmodium falciparum. Of the plants tested, 73% were
active (IC(50)<100 &mgr;g/ml). Three plants, Vernonia lasiopus, Rhamnus
prinoides and Ficus sur afforded extracts with IC(50) values ranging less than
30 &mgr;g/ml against both CQ-sensitive and resistant strains. Combination of
some extracts with CQ against the multi-drug resistant P. falciparum isolate
V1/S revealed some synergistic effect. The plant extracts with low IC(50) values
may be used as sources for novel antimalarial compounds to be used alone or in
combination with CQ.  PMID: 12648820 [PubMed - as supplied by publisher]
Trends Parasitol  2003 Mar;19(3):144-9 
Human migration, mosquitoes and the evolution of Plasmodium falciparum.
Hume JC, Lyons EJ, Day KP.
Peter Medawar Building for Pathogen Research, Dept of Zoology, University of
Oxford, OX1 3SY, Oxford, UK
To date, coalescent analysis of the Plasmodium falciparum genome sequence has
failed to provide a unifying theory regarding the parasite's evolution. While a
better understanding of the evolution of the malaria genome will undoubtedly
clarify the current controversy, the importance of the parasite's interplay with
both the human host and mosquito vector cannot be underestimated. Changes in the
population biology or ecology of either one of these species have consequences
for malaria transmission and this was never more apparent than in the
environmental changes brought about by the advent of agriculture. 
PMID: 12643998 
Trends Parasitol  2003 Mar;19(3):135-43 
The Plasmodium sporozoite journey: a rite of passage.
Kappe SH, Kaiser K, Matuschewski K.
Michael Heidelberger Division, Dept of Pathology, New York University School of
Medicine, 10016, New York, NY, USA
Sporozoites are the most versatile of the invasive stages of the Plasmodium life
cycle. During their passage within the mosquito vector and the vertebrate host,
sporozoites display diverse behaviors, including gliding locomotion and invasion
of, migration through and egress from target cells. At the end of the journey,
sporozoites invade hepatocytes and transform into exoerythrocytic stages,
marking the transition from the pre-erythrocytic to the erythrocytic part of the
life cycle. This article discusses recent work, mostly done with rodent malaria
parasites, that has contributed to a better understanding of the sporozoites'
complex biology and which has opened up new avenues for future sporozoite
research. PMID: 12643997 [PubMed - in process]
Trends Parasitol  2003 Mar;19(3):115-20 
Can primaquine therapy for vivax malaria be improved?
Baird JK, Rieckmann KH.
US Naval Medical Research Unit #2, American Embassy Jakarta, Fleet Post Office,
Asia-Pacific 96520-8132, USA
The incidence and range of endemic malaria caused by Plasmodium vivax has
expanded during the past 30 years. This parasite forms hypnozoites in the liver,
creating a persistent reservoir of infection. Primaquine (PQ), introduced 50
years ago, is the only drug available to eliminate hypnozoites. However, lengthy
treatment courses and follow-up periods are not conducive to assessing the
effectiveness of this drug in preventing relapses. Resistance to standard
therapy could be widespread. Studies are urgently needed to gauge this problem
and to determine the safety, tolerability and efficacy of shorter courses and
higher doses of PQ. PMID: 12643993 [PubMed - in process]
Trends Parasitol  2003 Mar;19(3):103-5 
The mosquito genome: perspectives and possibilities.
Land KM.
Sandler Center for Basic Research in Parasitic Diseases, University of
California, 94143, San Francisco, CA, USA
Anopheles gambiae is the mosquito vector responsible for transmitting Plasmodium
falciparum, a malaria parasite of humans. With the emergence of genome projects
for a variety of prokaryotic and eukaryotic microorganisms, there has been a
long-standing interest in sequencing the genomes of the malaria parasite and its
insect vector. This tour de force effort has now been completed and reported.
The alignment of putative orthologs in An. gambiae with those of Drosophila
melanogaster highlights several similarities and differences. These findings
could have implications in: (1) identifying new targets for insecticide
development; (2) strengthening our understanding of the developmental biology of
mosquitoes; and (3) possibly controlling pathogen transmission. A brief overview
of these interesting findings and the implications for further studies will be
discussed here. PMID: 12643988 [PubMed - in process]
J Infect  2003 Apr;46(3):164-72 
Does Infection with Human Immunodeficiency Virus Affect the Antibody
Responses to Plasmodium falciparum Antigenic Determinants in 
Asymptomatic Pregnant Women?
Ayisi JG, Branch OH, Rafi-Janajreh A, van Eijk AM, ter Kuile FO, Rosen DH, Kager
PA, Lanar DE, Barbosa A, Kaslow D, Nahlen BL, Lal AA.
Centre for Vector Biology & Control Research, Kenya Medical Research Institute,
Kisumu, Kenya
OBJECTIVES: HIV-seropositive pregnant women are more susceptible to malaria than
HIV-seronegative women. We assessed whether HIV infection alters maternal and 
cord plasma malarial antibody responses and the mother-to-infant transfer of
malaria antibodies.METHODS: We determined plasma levels of maternal and cord
antibodies [Immunoglobulin (IgG)] to recombinant malarial proteins [merozoite
surface protein 1 (MSP-1(19kD)), the erythrocyte binding antigen (EBA-175)], the
synthetic peptides [MSP-2, MSP-3, rhoptry associated protein 1 (RAP-1), and the
pre-erythrocytic stage, circumsporozoite protein (NANP)(5)] antigenic
determinants of Plasmodium falciparum; and tetanus toxoid (TT) by ELISA among
samples of 99 HIV-seropositive mothers, 69 of their infants, 102
HIV-seronegative mothers and 62 of their infants.RESULTS: The prevalence of
maternal antibodies to the malarial antigenic determinants ranged from 18% on
MSP3 to 91% on EBA-175; in cord plasma it ranged from 13% to 91%, respectively.
More than 97% of maternal and cord samples had antibodies to TT. In multivariate
analysis, HIV infection was only associated with reduced antibodies to (NANP)(5)
in maternal (P=0.001) and cord plasma (P=0.001); and reduced mother-to-infant
antibody transfer to (NANP)(5) (P=0.012). This effect of HIV was independent of
maternal age, gravidity and placental malaria. No consistent HIV-associated
differences were observed for other antigenic determinants.CONCLUSION: An effect
of HIV infection was only observed on one malarial antigenic determinant,
suggesting that the increased susceptibility to malaria among HIV-infected
pregnant women may not be explained on the basis of their reduced antibody
response to malaria antigens. PMID: 12643865 [PubMed - in process]
Malar J  2003 Feb 19;2(1):3 
Epidemiological models for the spread of anti-malarial resistance.
Koella J, Antia R.
Laboratoire de Parasitologie Evolutive, Universite P, & M, Curie, CNRS UMR 7103,
7 quai St, Bernard CC237, 75252 Paris, France. 
Email: [email protected]
BACKGROUND: The spread of drug resistance is making malaria control increasingly
difficult. Mathematical models for the transmission dynamics of drug sensitive
and resistant strains can be a useful tool to help to understand the factors
that influence the spread of drug resistance, and they can therefore help in the
design of rational strategies for the control of drug resistance. METHODS: We
present an epidemiological framework to investigate the spread of anti-malarial
resistance. Several mathematical models, based on the familiar Macdonald-Ross
model of malaria transmission, enable us to examine the processes and parameters
that are critical in determining the spread of resistance. RESULTS: In our
simplest model, resistance does not spread if the fraction of infected
individuals treated is less than a threshold value; if drug treatment exceeds
this threshold, resistance will eventually become fixed in the population. The
threshold value is determined only by the rates of infection and the infectious
periods of resistant and sensitive parasites in untreated and treated hosts,
whereas the intensity of transmission has no influence on the threshold value.
In more complex models, where hosts can be infected by multiple parasite strains
or where treatment varies spatially, resistance is generally not fixed, but
rather some level of sensitivity is often maintained in the population.
CONCLUSIONS: The models developed in this paper are a first step in
understanding the epidemiology of anti-malarial resistance and evaluating
strategies to reduce the spread of resistance. However, specific recommendations
for the management of resistance need to wait until we have more data on the
critical parameters underlying the spread of resistance: drug use, spatial
variability of treatment and parasite migration among areas, and perhaps most
importantly, cost of resistance. PMID: 12643812 
Arch Inst Pasteur Madagascar  2002;68(1-2):79-85 
Malaria in Madagascar [Article in French]
Raharimalala LA, Rabarijaona L, Randrianarivelojosia M, Razanavololo F, Rason
MA, Andrianantenaina HB, Andrianaivolambo L, Rakotoniaina JC, Leong Pock Tsi JM,
Rajaonarivelo E, Leon T, Duchemin JB, Ariey F.
Institut Pasteur de Madagascar, Groupe de Recherche sur le Paludisme, BP
1274-101 Antananarivo-Madagascar.
Madagascar is a tropical island affected by many natural disasters. The eastern
coastal zone--an area of perennial malaria transmission--is regularly exposed to
cyclones. Few malaria studies have been done in this area of Madagascar, and
none have examined the potential relationship between malaria and natural
disasters. A mobile team spent six weeks in the fields doing three lines of
research: an entomological study by catching mosquitoes and determining their
species: a therapeutic study of chloroquine (CQ) and sulphadoxine-pyrimethamine
(SP) according to a 14 days WHO protocol and also a study of physician's
diagnostic ability. Physicians were asked to make a presumptive clinical
diagnosis of all febrile patients, and these results were compared to those
obtained from blood smear examinations. The entomological study found three
major vectors species: Anopheles gambiae, An. funestus and An. mascarensis. The
therapeutic study showed that SP was 100% effective (n = 13) and only one case
of CQ treatment failure was recorded (1/15). Finally the diagnostic study
demonstrated that presumptive diagnosis of malaria based on the only clinical
signs leads to an over-estimation of malaria frequency. Over 68% (102/149) of
febrile patients were diagnosed by physicians to have malaria while only 52
(34.9%) were proven positive. Of the 47 patients diagnosed clinically as
malaria-negative, 12 (25.5%) turned out to be positive. Outbreaks of malaria
during or after natural disasters in Madagascar can be successfully treated with
either CQ or SP, but compliance may be better with SP since it requires only one
dose. Perhaps equally important in the context of natural disasters is to have
the capacity to make a definitive diagnosis, and the dipsticks should be made
available. PMID: 12643099 [PubMed - in process]
Arch Inst Pasteur Madagascar  2002;68(1-2):73-8 
Malaria policy in Madagascar [Article in French]
Randrianarivelojosia M, Rakotonjanabelo LA, Mauclere P, Ratsimbasoa A,
Raharimalala LA, Ariey F.
Institut Pasteur de Madagascar, Groupe de Recherche sur le Paludisme, BP
1274-101 Antananarivo-Madagascar.
To redefine strategy and policy to cure or to prevent malaria, there is a need
to get relevant and updated data on Plasmodium sp sensitivity level to
antimalarial drugs. Thus, in September 1999, the Madagascan Ministry of Health
and the Institut Pasteur de Madagascar (IPM) formed a network named RER for
malaria resistance surveillance. To alleviate the lack of experienced medical
teams within the health centres, and due to technical and logistic matters, as
part of the network activities, it was decided to give a start with the in vitro
studies which are carried out at IPM. In vitro sensitivity testing is done by
use of the isotopic method. Results from the study done in 2001 demonstrate that
the Madagascan P. falciparum isolates are susceptible to amodiaquine (n = 215),
to cycloguanil (n = 56), to pyrimethamine (n = 98) and to quinine (n = 214). One
isolate (1/110 i.e. 0.9%) of mefloquine-resistant phenotype is detected from the
Eastern region. P. falciparum susceptibility to chloroquine is satisfactory with
95.4% (206/216) of in vitro sensitive isolates. RER arises from the partnership
and collaboration between the Madagascan Ministry of Health and the IPM. The
network set-up is presented. The usefulness of the in vivo approach, and the in
vitro investigations (chemosusceptibility test and screening of mutations
accounting for resistance to chloroquine) to monitor the emergence and the
dissemination of drug-resistant parasites in Madagascar as well as in the
subregion of the Indian Ocean is discussed. PMID: 12643098 
Drug Chem Toxicol  2003 Feb;26(1):59-71 
Influence of chloroquine treatment and Plasmodium falciparum malaria
infection on some enzymatic and non-enzymatic antioxidant defense
indices in humans.
Farombi EO, Shyntum YY, Emerole GO.
Department of Biochemistry, Drug Metabolism and Toxicology, Research
Laboratories, College of Medicine, University of Ibadan, Nigeria.
Email: [email protected]
BACKGROUND: It is known that malaria infection is accompanied by increased
production of reactive oxygen species (ROS) and that malaria parasites are
sensitive to oxidative damage. This has been proved by the efficacy of some
antimalarial drugs that are known to act via generation of ROS when administered
clinically or experimentally. OBJECTIVE: There is lack of information on the
effect of chloroquine on the antioxidant defense systems of normal and malaria
infected humans. Since chloroquine has remained the mainstay of therapeutic
regimen in malaria endemic zones, the present investigation was therefore
undertaken to study the status of blood antioxidant defense mechanism, and
oxidative stress following chloroquine treatment in normal and plasmodium
infected humans. METHODS: Ten healthy persons (5 males and 5 females) with the
same age range (18-35 years) were taken as control group. Ten other individuals
were treated with 25 mg/kg body with chloroquine over three days. Ten patients
with malaria, not under antimalarial therapy were taken as another group, while
another set of 10 patients with malaria were treated with 25 mg/kg body weight
over three days. RESULTS: The activity of superoxide dismutase was increased by
23% in individuals treated with chloroquine compared to controls while the
activity of the enzyme decreased by 26% in malaria patients and by 43% in
malaria patients treated with chloroquine. In all the treatment groups, the
activities of catalase and glutathione peroxidase were lowered (P < 0.001).
Similarly the levels of vitamins A, C, and beta-carotene were decreased in the
treatment groups while plasma ceruloplasmin was increased in the groups.
Glutathione and cholesterol levels were decreased while malondialdehyde level
was increased significantly. CONCLUSION: Chloroquine treatment mediated
oxidative stress in the host and this effect was exacerbated in Plasmodium
falciparum infected patients administered with the drug. PMID: 12643041
Proc R Soc Lond B Biol Sci  2003 Mar 7;270(1514):545-54 
The de novo selection of drug-resistant malaria parasites.
White NJ, Pongtavornpinyo W.
Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok
10400, Thailand; and Centre for Tropical Diseases, Nuffield Department of
Clinical Medicine, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Antimalarial drug resistance emerges de novo predominantly in areas of low
malaria transmission. Because of the logarithmic distribution of parasite
numbers in human malaria infections, inadequately treated high biomass
infections are a major source of de novo antimalarial resistance, whereas use of
antimalarial prophylaxis provides a low resistance selection risk. Slowly
eliminated antimalarials encourage resistance largely by providing a selective
filter for resistant parasites acquired from others, and not by selecting
resistance de novo. The de novo emergence of resistance can be prevented by use
of antimalarial combinations. Artemisinin derivative combinations are
particularly effective. Ensuring adequate treatment of the relatively few
heavily infected patients would slow the emergence of resistance. PMID: 12641911 

Am J Trop Med Hyg  2003 Feb;68(2):186-90 
Human genetic polymorphisms and asymptomatic Plasmodium falciparum 
malaria in Gabonese schoolchildren.
Mombo LE, Ntoumi F, Bisseye C, Ossari S, Lu CY, Nagel RL, Krishnamoorthy R.
Centre International de Recherches Medicales de Franceville, Franceville, Gabon.
Email: [email protected]
Several studies have focused their attention on the relationship between host
genetic factors and susceptibility/resistance to severe malaria. However, there
is a paucity of information concerning the role of host genetic factors in
asymptomatic malaria, a form of low-grade Plasmodium falciparum infection
without clinical symptoms. We investigated in this study the potential
relationship between the host (human) genetic polymorphisms (glucose-6-phosphate
dehydrogenase [G6PD], mannose binding lectin [MBL], tumor necrosis factor alpha
[TNFalpha](-308) and (-238), and nitric oxide synthase 2 [NOS2](-954)) and the
prevalence and profile of asymptomatic P. falciparum infection in 158 Gabonese
schoolchildren. We found that G6PD A- heterozygous females (18 of 74) have a low
prevalence of asymptomatic malaria (38.9% versus 67.3%; P = 0.03, by chi-square
test). Children heterozygous for TNFalpha(-238) (25 of 156) carry high number of
diverse infecting parasite genotypes (2.5 versus 1.99; variance F = 3.05). No
statistically significant association was found between MBL, TNFalpha(-308), or
NOS2 polymorphisms and asymptomatic malaria. Upon combining our data on
asymptomatic forms with those from the literature for others forms, we conclude
that G6PD A- heterozygous females are protected against all forms of P.
falciparum malaria, and that the TNFalpha(-238A) allele confers protection
against clinical malaria. PMID: 12641410 
Am J Trop Med Hyg  2003 Feb;68(2):182-5 
Normal riboflavin status in malaria patients in Gabon.
Traunmuller F, Ramharter M, Lagler H, Thalhammer F, Kremsner PG, Graninger W,
Winkler S.
Department of Internal Medicine I, Division of Infectious Diseases, University
of Vienna, Vienna, Austria. Email: [email protected]
Previous publications reported commonly the occurrence of riboflavin deficiency
and a positive correlation between riboflavin status and parasitemia in patients
with Plasmodium falciparum malaria. In these studies, riboflavin status was
determined by erythrocyte glutathione reductase activation coefficients
(EGRACs). Inherited low erythrocyte glutathione reductase activity is highly
prevalent in malarial regions, however. To rule out falsely diagnosed riboflavin
deficiency in affected patients, we conducted an investigation using a
high-performance liquid chromatography method (HPLC) instead of the EGRAC
method. In 29 infants (age range, 1-5 years), 22 schoolchildren (age range, 6-12
years), and 33 adolescents and adults (age range, 13-74 years) from Lambarene,
Gabon, with acute P. falciparum malaria, plasma concentrations of riboflavin,
flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD) were measured
by HPLC. Results were correlated with parasite densities. Profiles of plasma
concentrations of all 3 flavin compounds were within the normal range in all
patients. Concentrations of free riboflavin were not different between the 3 age
groups. In adolescents and adults, FMN and FAD concentrations were higher than
in infants (P = 0.002 and P = 0.001) and schoolchildren (P = 0.003 and P =
0.002). Comparing children with hyperparasitemic and uncomplicated malaria, no
difference in the concentrations of either flavin compound was found. Neither
the concentrations of free riboflavin nor the concentrations of one of the
flavin nucleotides correlated with parasitemia within subgroups of age or of
children with uncomplicated and hyperparasitemic malaria. Our data indicate that
nutritional riboflavin deficiency might have been overestimated in previous
malaria studies and do not support a relationship between flavin concentrations
and parasitemia in P. falciparum malaria. PMID: 12641409 
Am J Trop Med Hyg  2003 Feb;68(2):177-81 
Strong association between house characteristics and malaria vectors in Sri
Konradsen F, Amerasinghe P, van der Hoek W, Amerasinghe F, Perera D, Piyaratne
Department of International Health, University of Copenhagen, Copenhagen,
The objective of this study was to determine whether house characteristics could
be used to further refine the residual insecticide-spraying program in Sri
Lanka. Indoor-resting mosquito densities were estimated in 473 houses based on
fortnightly collections over a two-and-a-half-year period. The type of house
construction and the exact location of all houses were determined. In a
multivariate analysis, distance of less than 750 meters between a house and the
main vector-breeding site was strongly associated with the presence of Anopheles
culicifacies in the house (odds ratio [OR] 4.8, 95% confidence interval [CI]
3.4-6.8) and to a lesser extent with the presence of An. subpictus (OR 1.4, 95%
CI 1.1-1.7). Poor housing construction also was an independent risk factor (OR
for An. culicifacies 1.3, 95% CI 1.0-1.9; OR for An. subpictus 1.3, 95% CI
1.0-1.6). It is recommended that a malaria control strategy focus on residential
areas within 750 meters of streams and rivers, with special attention given to
areas with the poorest type of house construction. PMID: 12641408
Am J Trop Med Hyg  2003 Feb;68(2):169-76 
Malaria transmission in urban sub-Saharan Africa.
Robert V, Macintyre K, Keating J, Trape JF, Duchemin JB, Warren M, Beier JC.
Institut de Recherche pour le Developpement, France. 
Email: [email protected]
The rapid increase in the world's urban population has major implications for
the epidemiology of malaria. A review of malaria transmission in sub-Saharan
African cities shows the strong likelihood of transmission occurring within
these sprawling cities, whatever the size or characteristics of their
bioecologic environment. A meta-analysis of results from studies of malaria
transmission in sub-Saharan Africa shows a loose linear negative relationship
between mean annual entomologic inoculation rates (EIR) and the level of
urbanicity. Few studies have failed to find entomologic evidence of some
transmission. Our results show mean annual EIRs of 7.1 in the city centers, 45.8
in periurban areas, and 167.7 in rural areas. The impact of urbanization in
reducing transmission is more marked in areas where the mean rainfall is low and
seasonal. Considerable variation in the level of transmission exists among
cities and within different districts in the same city. This article presents
evidence from past literature to build a conceptual framework to begin to
explain this heterogeneity. The potential for malaria epidemics owing to
decreasing levels of natural immunity may be offset by negative impacts of
urbanization on the larval ecology of anopheline mosquitoes. Malaria control in
urban environments may be simpler as a result of urbanization; however, much of
what we know about malaria transmission in rural environments might not hold in
the urban context. PMID: 12641407 
Am J Trop Med Hyg  2003 Feb;68(2):161-8 
Transmission of mixed Plasmodium species and Plasmodium falciparum
Arez AP, Pinto J, Palsson K, Snounou G, Jaenson TG, do Rosario VE.
Centro de Malaria e outras Doencas Tropicais, Instituto de Higiene e Medicina
Tropical, Universidade Nova de Lisboa, Lisboa, Portugal. 
Email: [email protected]
We studied malaria transmission by comparing parasite populations in humans and
mosquito vectors at the household level. Blood samples were collected from all
inhabitants for microscopic detection of gametocytes and polymerase chain
reaction analysis. The next morning, blood-fed resting mosquitoes were collected
inside the bed nets used by the individuals surveyed the previous afternoon.
After 8 days of maintenance, mosquitoes were dissected, and midguts and salivary
glands were recovered for polymerase chain reaction analysis. Results showed
that parasite distribution was the same in the 2 hosts when compared at each
household but was different when whole populations were analyzed. Different
associations of Plasmodium species seem to occur in humans (Plasmodium
falciparum/Plasmodium malariae) and mosquitoes (P. falciparum/Plasmodium ovale).
Regarding P. falciparum infections, a higher proportion of single-genotype
infections and less allele diversity are observed in mosquitoes than in humans.
PMID: 12641406 
Am J Trop Med Hyg  2003 Feb;68(2):159-60 
Case report: An unusual late relapse of Plasmodium vivax malaria.
Mangoni ED, Severini C, Menegon M, Romi R, Ruggiero G, Majori G.
Dipartimento di Medicina Interna, Seconda Universita di Napoli, Ospedale Gesu e
Maria, Naples, Italy.
We observed an unusual case of Plasmodium vivax malaria who presented with an
initial relapse four years after the primary infection. This occurred in
Cameroon, where the patient, a 56-year-old priest, acquired a mild form of
malaria and was treated with only chloroquine. Since he returned to Italy, he
had not experienced any malaria-like symptoms, had not visited any other areas
endemic for malaria, and had not received a blood transfusion. Blood smear
microscopy confirmed the presence of Plasmodium spp. parasites, but unclear
morphologic characteristics did not allow discrimination between P. vivax and P.
ovale. A nested polymerase chain reaction-based molecular analysis identified P.
vivax as the plasmodial species responsible. This case emphasizes the importance
of taking into account the possibility of a very late initial relapse of P.
vivax malaria and the relevant issues in terms of infection control.
PMID: 12641405 
Am J Trop Med Hyg  2003 Feb;68(2):153-8 
Descriptive study on the efficacy and safety of artesunate suppository in
combination with other antimalarials in the treatment of severe malaria in
Awad MI, Alkadru AM, Behrens RH, Baraka OZ, Eltayeb IB.
Department of Pharmacology, Faculty of Pharmacy, University of Khartoum,
Khartoum, Sudan.
Documentation on the efficacy of artesunate in Africa is limited, and no
experience of artesunate use in Sudan is documented. Severe malaria in rural
areas of Sudan, where facilities for the safe and effective use of parenteral
quinine are lacking, is a frequent problem. Early treatment with artesunate
suppositories would provide a simple method for use by unskilled staff and would
be an alternative approach to treat malaria in settings with poor resources. We
describe a hospital-based study of rectal artesunate in 100 adult patients with
severe falciparum malaria with a dose derived from pharmacokinetic data (200 mg
every 8 hours) over 3 days, which halted progression of severe disease and had a
low fatality rate. The dosage schedule led to a rapid clinical response and
reduced parasite clearance and fever subsidence times of (31.5 +/- 10.1 hours)
and (31.4 +/- 11.1 hours). The sequential treatment of rectal artesunate with
either doxycycline or pyrimethamine/sulfadoxine or mefloquine resulted in
similar clinical cure rates of around 100%, and the combination of artesunate
with either doxycycline or pyrimethamine/sulfadoxine was equally effective as
mefloquine in preventing recrudescence. There were no significant adverse
effects or signs of toxicity related to the treatment observed during the 28-day
follow-up. The combination regimens could be used in areas where there is
limited access to parenteral therapy for malaria. PMID: 12641404 
Am J Trop Med Hyg  2003 Feb;68(2):147-52 
Recrudescence in artesunate-treated patients with falciparum malaria is
dependent on parasite burden not on parasite factors.
Ittarat W, Pickard AL, Rattanasinganchan P, Wilairatana P, Looareesuwan S, Emery
K, Low J, Udomsangpetch R, Meshnick SR.
Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol
University, Bangkok, Thailand. 
Artemisinin derivatives are first-line antimalarial drugs in Thailand. No firm
evidence of clinically relevant artemisinin resistance exists. When used as
monotherapy, artesunate has been associated with a high treatment failure
(recrudescence) rate, which could be due to low-level artemisinin resistance. To
understand the causes of recrudescence, we retrospectively studied a cohort of
104 malaria patients treated with artesunate monotherapy, 32 of whom
recrudesced. There was no difference in in vitro artesunate sensitivities
between 6 nonrecrudescent isolates and 16 paired admission and recrudescent
isolates. Paired admission and recrudescent isolates from 10 patients were
genotyped; only 3 had pfmdr1 mutations. Patients with admission parasitemias
>10,000 per microl had a 9-fold higher likelihood of recrudescence (adjusted
odds ratio) compared with patients with lower parasitemias. This study suggests
(1) recrudescence after treatment with artesunate is not the result of inherent
parasite resistance, and (2) admission parasitemia may be useful in choosing
therapeutic options. PMID: 12641403
Am J Trop Med Hyg  2003 Feb;68(2):140-2 
Drug-resistant malaria in Bangladesh: an in vitro assessment.
Noedl H, Faiz MA, Yunus EB, Rahman MR, Hossain MA, Samad R, Miller RS, Pang LW,
Wongsrichanalai C.
U.S. Army Medical Component, Armed Forces Research Institute of Medical
Sciences, Bangkok, Thailand.
Forty-four Plasmodium falciparum isolates from Bangladesh and 22 from western
Thailand were successfully tested for their drug susceptibility. High degrees of
resistance were observed against chloroquine with geometric mean IC50s of 114.25
and 120.5 nM, respectively, for Bangladesh and western Thailand. Most isolates
from both sites were sensitive to quinine, and all were sensitive to artesunate.
Many isolates were considered in vitro resistant to mefloquine, but the
geometric mean IC50 for the Thai isolates (98.79 nM) was 1.6 times (P = 0.002)
higher than that of isolates from Bangladesh (60.3 nM). The high prevalence of
in vitro mefloquine resistance in Bangladesh suggests that close surveillance is
necessary to delay widespread multidrug resistant problems in the area.
Am J Trop Med Hyg  2003 Feb;68(2):127-32 
Comparative efficacy of aminoquinoline-antifolate combinations for the
treatment of uncomplicated falciparum malaria in Kampala, Uganda.
Gasasira AF, Dorsey G, Nzarubara B, Staedke SG, Nassali A, Rosenthal PJ, Kamya
Makerere University Medical School, Kampala, Uganda.
Resistance to chloroquine (CQ) requires its replacement as first-line therapy
for uncomplicated malaria in much of Africa. Combination therapy may improve
efficacy and delay the selection of resistant malaria parasites. Combinations of
sulfadoxine-pyrimethamine (SP) with 4-aminoquinolines offer affordable and
available alternatives to CQ. We conducted a randomized, single-blinded trial to
compare the efficacy of SP monotherapy with combinations of SP and either CQ or
amodiaquine (AQ) for the treatment of uncomplicated falciparum malaria in
patients over 6 months of age in Kampala, Uganda. Of the 448 patients enrolled,
428 (95%) completed follow-up. Clinical treatment failure after 14 days occurred
in 21/140 (15.0%, 95% CI 9.5-22.0%) SP-treated, 11/152 (7.2%, 95% CI 3.7-12.6%)
SP/CQ-treated, and 0/136 (0%, 95% CI 0-2.7%) SP/AQ-treated patients. Combination
therapies were safe and offered superior efficacy to SP monotherapy. SP/AQ was the 
most efficacious. This low-cost combination regimen may provide an optimal alternative
to CQ for the treatment of uncomplicated malaria in Uganda.
PMID: 12641399 
Vaccine  2003 Apr 2;21(15):1650-7 
Expression of malaria transmission-blocking vaccine antigen Pfs25 in Pichia
pastoris for use in human clinical trials.
Zou L, Miles AP, Wang J, Stowers AW.
Malaria Vaccine Development Unit, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, 20852, Rockville, MD, USA
In previously published studies, Saccharomyces cerevisiae recombinant protein
expression systems have been employed to express the malaria parasite antigen
Pfs25, a candidate transmission-blocking vaccine antigen against Plasmodium
falciparum malaria. However, despite having been in two Phase 1 trials, the
recombinant Pfs25 so produced (previously called TBV25H) exists as a mixture of
two monomeric protein conformational forms, Pfs25H-A and Pfs25H-B. In this
study, we optimized the expression and purification of the two Pfs25H conformers
in S. cerevisiae, and characterized their biochemical and antigenic properties,
immunogenicities, and transmission-blocking activities. Pfs25H-A is apparently
homogeneous, and has the correct conformation as measured by monoclonal antibody
recognition. It is, however, expressed at a low yield of only 0.19mg/l. By
contrast, Pfs25H-B is produced as a heterogeneous population of molecules that
do not seem to have the correct conformation. Nonetheless, both forms appear
equally effective in their ability to produce transmission-blocking antibodies
in mice. To address the low yield seen with S. cerevisiae, we also expressed
Pfs25 in Pichia pastoris. P. pastoris is apparently superior to S. cerevisiae in
producing higher yield, immunologically more potent, biologically more active
East Afr Med J  2002 Jul;79(7):343-6 
Prophylactic effect of multi-herbal extract 'Agbo-Iba' on malaria induced in
Nwabuisi C.
Department of Medical Microbiology and Parasitology, Faculty of Health Sciences,
University of Ilorin, P.M.B. 1515, Ilorin, Nigeria.
OBJECTIVE: To determine the efficacy of a multi-herbal preparation extract of
'Agbo-Iba' on rodent malaria induced in mice. DESIGN: An experimental design in
which mice were divided into four groups A,B,C,D representing control,
prophylactic, chloroquine and 'Agbo-Iba' groups respectively. Each mouse was
intraperitoneally inoculated with Plasmodium yoelii nigeriensis and treated with
oral herbal extract or chloroquine syrup depending on group. SETTING: College of
Medicine of the University of Lagos Medical Microbiology and Parasitology
Laboratory. SUBJECTS: One hundred and twenty male and female albino mice aged
10-12 weeks with an average weight of 25 grams. MAIN OUTCOME MEASURES: The
herbal extract was effective, preventing the development of parasitaemia in the
prophylactic group of mice. RESULTS: After intraperitoneal inoculation of
Plasmodium yoelii nigeriensis, a prepatent period of two days was observed
before parasitaemia was established in all but the prophylactic group of mice.
Induced infection was promptly aborted with oral chloroquine treatment in group
C, while in groups A and D, infection terminated fatally. Group B mice appeared
normal throughout the duration of investigation with 100% survival rate.
CONCLUSION: 'Agbo-Iba' extract has some prophylactic action against malaria
induced in mice with no apparent significant side effects. PMID: 12638827 
East Afr Med J  2002 May;79(5):237-41 
In-vitro sensitivity of Plasmodium falciparum to chloroquine, halofantrine,
mefloquine and quinine in Madagascar.
Randrianarivelojosia M, Ratsimbasoa A, Randrianasolo L, Randrianarijaona A,
Jambou R.
Unite d'Immunologie, Institut Pasteur de Dakar BP 220 Dakar, Senegal.
OBJECTIVE: To determine how sensitive Plasmodium falciparum is to the major
antimalarial drugs in Madagascar. DESIGN: Assessment of Plasmodium falciparum
isolates sensitivity to antimalarials, by use of the in-vitro radioisotope
method. SETTING: Ankazobe and Saharevo in the foothill areas; and Toamasina and
Tolagnaro in the coastal areas (between January 1998 and November 1999).
SUBJECTS: Primary Plasmodium falciparum isolates from patients with
uncomplicated malaria attack. RESULTS: Between January 1998 and November 1999,
of the 293 in-vitro tests done with at least one antimalarial, 70% (205/293)
were interpretable. As there was no significant difference between results from
the four study sites, the data have been expressed as a whole. All of the
successfully tested isolates were sensitive to halofantrine (n = 56) and to
quinine (n = 199), 5.8% (12/205) of the isolates were resistant to chloroquine
and 2% (4/199) to mefloquine. The geometric mean IC50 was 0.3 microg/L for
halofantrine (95% CI = 0.1-0.4 microg/L); 9.4 microg/L for chloroquine (95% CI =
7.3-10.8 microg/L); 3.8 microg/L for mefloquine (95% CI = 3.3-4.3 microg/L); and
26.8 microg/L for quinine (95% CI = 24.3-29.4 microg/L). The low positive
correlation found between halofantrine and chloroquine IC50s (n = 56; r = 0.41,
P = 0.002) suggests a risk of cross-resistance between these two drugs.
CONCLUSION: The degree and frequency of chloroquine resistance in-vitro is
stationary in Madagascar compared to previous results during the last decade.
The in-vitro sensitivity of P. falciparum to quinine, mefloquine and
halofantrine encourages the use of these drugs as alternative in case of
chloroquine treatment failure. Nevertheless, it is important to maintain and to
extend malaria and drug sensitivity surveillance in Madagascar.
PMID: 12638806 
Malar J  2003 Feb 17;2(1):2 
Observations on the swarming and mating behaviour of Anopheles funestus
from southern Mozambique.
Charlwood J, Thompson R, Madsen H.
Danish Bilharziasis Laboratory, 1-D Jaergersborg Alle, DK2920 Charlottenlund,
Denmark. Email: [email protected]
BACKGROUND: Control of malaria by the release of genetically modified mosquitoes
refractory to transmission is now becoming a possibility. In many areas of
Africa, Anopheles gambiae is found together with an equally important vector,
An. funestus. Given their sympatry and the likelihood of a similar mating period
some aspects of the mating behaviour of An. gambiae s.l. and An. funestus are
likely to differ. We therefore attempted to characterise the swarming behaviour
of An. funestus and to determine if any aspects of the observed behaviour
differed from that recorded for the M form of An. gambiae from Sao Tome.
METHODS: In March - May 2002 the swarming, mating, house exiting and resting
behaviour of Anopheles funestus was studied by direct observation in Mozambique.
Swarming males and insects in copula were collected by sweep net. Wing lengths
of males collected resting, exiting houses, swarming and mating were measured
and the wingbeat frequency distribution of individual insects, in free flight
confined inside netting covered paper cups, was also determined. RESULTS:
Mono-specific swarms occurred at sunset in relatively open areas close to houses
used for resting. Mating pairs were seen 11 PlusMinus; 3.7 min after the start
of swarming. The number of total pairs observed being inversely proportional to
the time difference between the start of swarming and the first pairing. The
great majority of females mated before feeding. Male or female size did not
appear to affect mating success or other behaviours. During the study, ambient
temperatures decreased and female, but not male, wing size increased. At 516 Hz,
the flight tone of female An. funestus was similar to the 497 Hz of the local
An. gambiae. Males dispersed if light or dark artificial horizontal markers were
placed underneath naturally occurring swarms. CONCLUSION: Differential response
to markers would be sufficient for swarming in An. funestus and An. gambiae s.l.
to occur in distinct sites. PMID: 12636875 
Parasitology  2003 Feb;126(Pt 2):103-12 
The effects of host immunity on virulence-transmissibility relationships in the
rodent malaria parasite Plasmodium chabaudi.
Mackinnon MJ, Read AF.
Institute of Cell, Animal and Population Biology, University of Edinburgh, West
Mains Road, Edinburgh EH9 3JT, Scotland. 
Email: [email protected]
Here we examined the impact of host immunity on relationships between parasite
virulence, transmission rate, intrinsic growth rate and host recovery rate in
the rodent malaria parasite, Plasmodium chabaudi. Groups of naive and immunized
mice were infected with 1 of 10 cloned lines of parasites and their infection
dynamics were monitored for 19 days. We found that (1) host immunity reduced the
growth rate, virulence, transmission rate and infection length, with a
consequent 3-fold reduction in life-time transmission potential, (2) clone means
for these traits ranked similarly across naive and immunized mice, (3)
regression slopes of transmission potential on growth rate, virulence and
infection length were similar in naive and immunized mice, (4) virulence and
infection length were positively correlated in immunized but not naive mice, and
(5) for a similar level of parasite growth rate and virulence, transmission
potential and infection length were lower in immunized than naive mice. Thus
host immunity reduced all these fitness traits in a manner consistent with
direct parasite-driven biological links among them. These results support the
basic assumption underlying our theory that predicts that anti-disease vaccines
will select for higher virulence in those microparasites for which virulence is
integrally linked to transmission. PMID: 12636347 
Pediatr Infect Dis J  2003 Mar;22(3):251-256 
Safety and therapeutic efficacy of artesunate suppositories for treatment of
malaria in children in Papua New Guinea.
Karunajeewa HA, Kemiki A, Alpers MP, Lorry K, Batty KT, Ilett KF, Davis TM.
BACKGROUND Although suppositories of artemisinin derivatives may be a valuable
option for treatment of malaria in children when circumstances prevent oral and
parenteral therapy, few confirmatory data have been published.METHODS We
assessed the safety and efficacy of rectal artesunate in 47 children ages 5 to
10 years with uncomplicated malaria acquired in a hyperendemic area of Papua New
Guinea. Thirty were symptomatic and had parasitemia >2000/&mgr;l (Group 1), 12
had and either a parasitemia <2000/&mgr;l or minimal/no symptoms (Group 2) and
5 had (Group 3). Each child received rectal artesunate 10 to 15 mg/kg at 0 and 12
h. After monitoring for 24 h, chloroquine plus sulfadoxine/pyrimethamine was
given, and the patient discharged.RESULTS Artesunate suppositories were
well-tolerated. After 24 h only one child (from Group 1) had persistent
parasitemia, and only one (from Group 3) had not defervesced. These two children
received intramuscular quinine and recovered uneventfully. Three Group 2
children redeveloped fever and tachycardia at 24 h, but each responded to simple
supportive measures and remained aparasitemic.CONCLUSIONS Intrarectal artesunate 
is safe, effective initial treatment for uncomplicated malaria in children. A
transient fever spike can sometimes occur after parasite clearance. We recommend
that children with uncomplicated malaria receive two doses of >/=10 mg/kg rectal
artesunate within the first 24 h. PMID: 12634587 
Int J Parasitol  2003 Feb;33(2):175-83 
Influence of CD4(+)CD25(+) T cells on Plasmodium berghei NK65 infection in
BALB/c mice.
Long TT, Nakazawa S, Onizuka S, Huaman MC, Kanbara H.
Department of Protozoology, Institute of Tropical Medicine, Nagasaki University,
1-12-4 Sakamoto, Nagasaki 852-8523, Japan
CD4(+) T cells co-expressing CD25 (CD4(+)CD25(+) T cells) have been identified
as immunoregulatory suppressors modulating autoimmune response. Beside that,
autoimmune response was supposed to be associated with malaria infection. Based
on these data, we hypothesised that CD4(+)CD25(+) T cells may influence
protective immunity to malaria parasites, while suppressing autoimmune response
arising throughout the course of malarial infection. To test this possibility,
we evaluated the kinetics of CD4(+)CD25(+) T cells during malaria infection and
investigated the influence of CD25 depletion by anti-mouse CD25 monoclonal
antibody (PC61) on the infection, using a mouse model of premunition to
Plasmodium berghei NK65 malaria. The results showed that, during exacerbation of
P. berghei NK65 infection, the proportion of CD4(+)CD25(+) T cells among CD4(+)
T cells decreased, although that of CD4(+) T cells increased. CD25 depletion
clearly delayed the growth of parasitaemia during parasite challenge,
particularly in immunised mice. These findings demonstrated that CD4(+)CD25(+) T
cells are able to influence protective immunity underlying premunition to P.
berghei NK65 parasites. PMID: 12633655
Parasitol Res  2003 Mar;89(5):371-4 
Design and development of an immunosensor for the detection of malaria 
in field conditions.
Mya M, Saxena K, Roy A, Roy B.
Centre for Biomedical Engineering, Indian Institute of Technology, New Delhi
110016, India.
Eradication of malaria in Southeast Asian countries is still a distant goal, due
to the absence of a simple, rapid and inexpensive diagnostic technique. Here, an
immunosensor for the photometric detection of malaria, the malaria-detecting
immunosensor (MDI), is developed to detect Plasmodium falciparum malarial
antibodies in human blood. The method uses the principle of laser
light-scattering by latex bead agglutinates in media monitored by a
light-detecting device. Agglutination is induced by mixing antigen-coated latex
beads with serum antibodies. Immunoreactions are measured in terms of the
Tyndall effect in the transmitted beam detected by photodiodes. MDI sensitivity
and specificity are compared with the results of enzyme-linked immunoabsorbent
assay and laser light-scattering immunoassay techniques, which show that it is a
good and sensitive monitoring device.
Parasitol Res  2003 Mar;89(5):354-7 
Comparison of three antigen detection tests for diagnosis and follow-up of
falciparum malaria in travellers returning to Berlin, Germany.
Grobusch MP, Hanscheid T, Gobels K, Slevogt H, Zoller T, Rogler G, Teichmann D.
Department of Parasitology, Institute of Tropical Medicine, Eberhard Karls
University, Wilhelmstrasse 27, 72074 Tuebingen, Germany,
Email: [email protected]
We determined the sensitivity and specificity of three rapid
immunochromatographic malarial antigen detection test systems (RDTs) for the
detection of Plasmodium falciparumand assessed the quality of follow-up results.
ParaSight-F and ICT Malaria detect histidine-rich protein-2 (HRP-2), whereas
OptiMal detects plasmodial lactate dehydrogenase (pLDH). ParaSight-F performed
with 95.1% sensitivity and 97.1% specificity (554 patients tested of whom 144
had falciparum malaria). ICT Malaria performed with 95.7% sensitivity and 99.2%
specificity (718 patients tested of whom 184 had falciparum malaria). OptiMal
performed with 76.2% sensitivity and 99.7% specificity (539 patients tested of
whom 130 had falciparum malaria). In follow-up investigations, HRP-2 did not
appear to be a useful antigen due to its long half-life, whereas pLDH offers a
reasonable correlation with the presence of viable parasites in those cases
initially detected. We therefore conclude that a combination of both antigens
might be the best option for creating a reliable RDT for the diagnosis of
falciparum malaria.
J Pharm Pharmacol  2003 Feb;55(2):193-8 
Therapeutic equivalence of a low dose artemisinin formulation in falciparum
malaria patients.
Wong JW, Yuen KH, Nagappan S, Shahul WS, Ho SS, Gan EK, Toh WT.
School of Pharmaceutical Sciences, University of Science Malaysia, Penang,
We have evaluated the therapeutic equivalence of a beta-cyclodextrin-artemisinin
complex at an artemisinin dose of 150 mg, with a commercial reference
preparation, Artemisinin 250 at a recommended dose of 250 mg. One hundred
uncomplicated falciparum malarial patients were randomly assigned to orally
receive either beta-cyclodextrin-artemisinin complex (containing 150 mg
artemisinin) twice daily for five days or the active comparator (containing 250
mg artemisinin) twice daily for five days. The patients were hospitalized for
seven days and were required to attend follow up assessments on days 14, 21, 28
and 35. All patients in both treatment groups were cured of the infection and
achieved therapeutic success. At day seven of treatment, all patient blood was
clear of the parasites and the sublingual temperature of all patients was less
than 37.5 degrees C. Moreover, the parasite clearance time in both treatment
groups was similar, being approximately three days after initiation of
treatment. Comparable plasma artemisinin concentrations were observed between
patients in both treatment groups at 1.5 and 3.0 h, although slightly higher
levels were obtained with patients in the beta-cyclodextrin-artemisinin
complex-treated group. The beta-cyclodextrin-artemisinin complex at a dose of
150 mg artemisinin was therapeutically equivalent to 250 mg Artemisinin 250.
Additionally, patients receiving beta-cyclodextrin-artemisinin complex showed
less variability in their plasma artemisinin concentrations at 1.5 h
post-dosing, which suggested a more consistent rate of drug absorption.
PMID: 12631411
Trop Med Int Health  2003 Mar;8(3):242-50 
Hospital costs of high-burden diseases: malaria and pulmonary tuberculosis in
a high HIV prevalence context in Zimbabwe.
Hongoro C, McPake B.
Department of Public Health and Policy, London School of Hygiene and Tropical
Medicine, UK.
This paper explores the measurement of hospital costs and efficiency in a
context where data is scarce, incomplete or of poor quality. It argues that
there is scope for using tracers to examine and compare hospital cost structures
and relative efficiency in such contexts. Two high-burden diseases, malaria and
pulmonary tuberculosis, are used as tracers to calculate the average costs of
inpatient care at selected tertiary hospitals. This study shows that it is
feasible to prospectively collect cost data for specific diseases and explore in
detail both patient cost distribution and susceptible areas for efficiency
improvement. The present study found that the critical source of efficiency
variation in public hospitals in Zimbabwe lies in the way hospital beds are
Trop Med Int Health  2003 Mar;8(3):202-3 
Clinical efficacy of chloroquine in young children with uncomplicated falciparum 
malaria - a community-based study in rural Burkina Faso.
Muller O, Traore C, Kouyate B.
Department of Tropical Hygiene and Public Health of the
Ruprecht-Karls-University Heidelberg, Heidelberg, Germany Centre de Recherche en
Sante de Nouna, Nouna, Burkina Faso.
We report on a 14-day study on the efficacy of chloroquine for treating
uncomplicated falciparum malaria in young children of a malaria holoendemic area
in rural Burkina Faso. In this community-based study, the overall treatment
failure rate was 12/120 (10%), with no differences between villages. This
supports the evidence for a still sufficient efficacy of chloroquine in
north-western Burkina Faso. PMID: 12631308
Trop Med Int Health  2003 Mar;8(3):196-201 
A health facility based case-control study of effectiveness of insecticide
treated nets: potential for selection bias due to pre-treatment with
Webster J, Chandramohan D, Freeman T, Greenwood B, Kamawal AU, Rahim F, Rowland
London School of Hygiene and Tropical Medicine, UK HealthNet International,
Peshawar, Pakistan.
Case control studies offer an attractive way to assess the effectiveness of
insecticide treated nets (ITN) under programme conditions but have the drawback
of being susceptible to bias in the choice of controls. We evaluated the
potential for pre-treatment with chloroquine to result in misclassification of
cases and controls and affect estimates of ITN effectiveness in case control
studies in urban and rural clinics in Eastern Afghanistan. During the one-month
study, use of ITN showed no effect against malaria in the urban clinic (adjusted
odds ratio OR 1.08; 95% CI 0.73-1.6) and the protective effect seen in the rural
clinic was not significant (OR 0.62; 95% CI 0.2-2.4). Levels of pre-treatment
were high in both clinics: 24% in urban and 19% in rural clinic attenders. In
the urban clinic attenders the level of pre-treatment between bed net users and
non-users was not significantly different (OR 1.07, 95% CI 0.70-1.64); therefore
the misclassification of cases as controls did not introduce any selection bias.
Amongst rural clinic attenders, bed net users were less likely to pre-treat with
chloroquine than users (OR 0.33, 95% CI 0.14-0.77); this introduced a selection
bias that resulted in an underestimation of the effectiveness of bed nets. Case
control studies using health facility data are liable to selection bias
especially in areas of high pre-treatment rates with chloroquine. Generalisation
of results over a wide geographic region, or between urban and rural settings,
may not be appropriate. PMID: 12631307
Trans R Soc Trop Med Hyg  2002 Nov-Dec;96(6):674-6 
Highly pyrimethamine-resistant alleles of dihydrofolate reductase in isolates
of Plasmodium falciparum from Tanzania.
Hastings MD, Bates SJ, Blackstone EA, Monks SM, Mutabingwa TK, Sibley CH.
Department of Genetics, Box 357360, University of Washington, Seattle, WA
98195-7360, USA.
In 2000 we used a sensitive technique to examine 9 isolates from malaria
patients in Muheza, Tanzania who had failed treatment with
sulfadoxine-pyrimethamine (SP). Three isolates carried, at low levels, the
leucine to isoleucine change at amino acid 164 that is associated with clinical
failure of SP. Numerous other highly resistant alleles were also observed.
PMID: 12630380 
Bioorg Med Chem  2003 Apr;11(7):1235-46 
New potent C(2)-Symmetric malaria plasmepsin I and II inhibitors.
Oscarsson K, Oscarson S, Vrang L, Hamelink E, Hallberg A, Samuelsson B.
Department of Organic Chemistry, Arrhenius Laboratory, Floor 6, Stockholm
University, S-106 91, Stockholm, Sweden
A series of malaria plasmepsin (Plm) I and II inhibitors containing a
C(2)-symmetric core structure have been synthesised and tested for protease
inhibition activity. These compounds can be prepared using a straightforward
synthesis involving a phenol nucleophilic ring opening of a diepoxide. Exemplar
compounds synthesised exhibited remarkable inhibitory activity against both Plm
I and II, notably 15c with K(i) values of 2.7nM and 0.25nM respectively, as well
as showing >100-fold selectivity against Cathepsin D. PMID: 12628651 
Biochimie  2002 Dec;84(12):1181-8 
Protection against experimental P. falciparum malaria is associated with 
short AMA-1 peptide analogue alpha-helical structures.
Cubillos M, Salazar LM, Torres L, Patarroyo ME.
Fundacion Instituto de Inmunologia de Colombia (FIDIC), Carrera 50, No. 26-00
Bogota, Colombia
Apical membrane antigen-1 (AMA-1) is an integral Plasmodium falciparum malaria
parasite membrane protein. Peptides having high activity binding to human red
blood cells have been identified in this protein. One of them, peptide 4325,
with the amino acid sequence MIKSAFLPTGAFKADRYKSH, for which critical binding
residues have already been defined (underlined), is conserved and
non-immunogenic. Its critical binding residues were changed for amino acids
having similar mass but different charge to change such immunological
properties. These changes rendered some peptides immunogenic and protective
against experimental challenge in Aotus monkeys. Three-dimensional models of
peptide 4325 and its analogues, 20032 and 20034, were calculated from NMR
experiments with distance geometry and restrained molecular dynamic methods.
Non-immunogenic, non-protective peptide 4325 showed differences in its secondary
structure with respect to protective, immunogenic peptides 20032 and 20034. Such
data suggest that these modifications could have converted non-immunogenic
peptides into immunogenic, protective ones, making them excellent candidates for
a multi-component subunit synthetic malaria vaccine.
PMID: 12628294 [PubMed - in process]
J Immunol  2003 Mar 15;170(6):3195-203 
The Dendritic Cell-Specific Chemokine, Dendritic Cell-Derived CC 
Chemokine 1, Enhances Protective Cell-Mediated Immunity to Murine Malaria.
Bruna-Romero O, Schmieg J, Del Val M, Buschle M, Tsuji M.
Department of Medical and Molecular Parasitology, New York University School of
Medicine, New York, NY 10010. Centro Nacional de Microbiologia, Instituto de
Salud Carlos III, Madrid, Spain. Intercell AG, Vienna, Austria.
Cell-mediated immunity plays a crucial role in the control of many infectious
diseases, necessitating the need for adjuvants that can augment cellular immune
responses elicited by vaccines. It is well established that protection against
one such disease, malaria, requires strong CD8(+) T cell responses targeted
against the liver stages of the causative agent, Plasmodium spp. In this report
we show that the dendritic cell-specific chemokine, dendritic cell-derived CC
chemokine 1 (DC-CK1), which is produced in humans and acts on naive lymphocytes, 
can enhance Ag-specific CD8(+) T cell responses when coadministered with either 
irradiated Plasmodium yoelii sporozoites or a recombinant adenovirus expressing 
the P. yoelii circumsporozoite protein in mice. We further show that these
enhanced T cell responses result in increased protection to malaria in immunized
mice challenged with live P. yoelii sporozoites, revealing an adjuvant activity
for DC-CK1. DC-CK1 appears to act preferentially on naive mouse lymphocytes, and
its adjuvant effect requires IL-12, but not IFN-gamma or CD40. Overall, our
results show for the first time an in vivo role for DC-CK1 in the establishment
of primary T cell responses and indicate the potential of this chemokine as an
adjuvant for vaccines against malaria as well as other diseases in which
cellular immune responses are important. PMID: 12626578
Ann Trop Med Parasitol  2002 Dec;96 Suppl 2:143-52 
Limitation and facilitation in the vectors and other aspects of the dynamics
of filarial transmission: the need for vector control against 
Anopheles-transmitted filariasis.
Pichon G.
Institut de Recherche pour le Developpement (IRD), Laboratoire d'Informatique
Appliquee, 32 Avenue Henri Varagnat, 93143 Bondy Cedex, France.
In certain filaria-mosquito combinations, the number of infective, third-stage
larvae (L(3)) that develop in a mosquito is not proportional to the number of
microfilariae (mff) ingested by that mosquito. As the number of mff ingested
increases, the yield of L(3) per microfilaria may either increase (in a process
known as 'facilitation') or decrease (in a process known as 'limitation'). Each
ingested microfilaria that is successful (in terms of reaching the haemocoel)
increases (facilitation) or decreases (limitation) the 'permeability' of the
stomach wall for the next microfilaria. Limitation is seen in some culicine
mosquitoes, especially the Aedes spp. that transmit Wuchereria bancrofti, which,
in consequence, become relatively more efficient as vectors as they ingest fewer
mff. This phenomenon makes the interruption of filarial transmission by Aedes
spp. particularly difficult. As the survival of anopheline mosquitoes is
adversely affected by filarial infection, the use of mass drug administrations
(MDA) to reduce the prevalence and intensity of microfilaraemias may increase
the mean lifespan of some of the local Anopheles species. If these same species
also act as vectors of malarial parasites, effective, drug-based control of W.
bancrofti may worsen the problem posed by malaria. Therefore, wherever malaria
and bancroftian filariasis are co-endemic and caused by parasites transmitted by
the same species of mosquito, MDA should be augmented by interventions (use of
bednets or house-spraying) against adult Anopheles.
PMID: 12625927 
East Afr Med J  2002 Sep;79(9):485-90 
Impact of cattle keeping on human biting rate of anopheline mosquitoes and
malaria transmission around Ziway, Ethiopia.
Seyoum A, Balcha F, Balkew M, Ali A, Gebre-Michael T.
Institute of Pathobiology, Faculty of Medicine, Addis Ababa University, P.O. Box
1176, Addis Ababa, Ethiopia.
OBJECTIVE: To assess the impact of livestock keeping on the human biting rate
(HBR) of anopheline mosquitoes and malaria transmission around Ziway in the
middle course of the Ethiopian Rift Valley. DESIGN: As a passive experiment, man
landing captures were done in homesteads with mixed dwelling, separate cattle
shed and without livestock; and as an active experiment, captures were in
experimental tukuls (huts) of cattle, goats, and without livestock. Parasite and
spleen rates of children were compared among those residents under variable
living conditions mentioned for passive experiment. SUBJECTS: For entomological
study, human-baits were used for man-landing captures of mosquitoes. Study
subjects for parasitological and clinical studies were children below 10 years
old. MAIN OUTCOME MEASURES: Human-biting rate (HBR) of anopheline mosquitoes; 
and the parasite and spleen rates of the study subjects in different living conditions.
RESULTS: In the passive experiment, the mean HBR of Anopheles
arabiensis in mixed dwelling, separate cattle shed and without livestock was
8.45, 4.64 and 5.97, respectively. Similarly, the HBR of An. pharoensis was
2.88, 1.79 and 1.61, respectively. In the active experiment, the mean HBR of An.
arabiensis in tukuls with cattle, goats, and without livestock was 3.50, 3.38
and 1.43 respectively; while that of An. pharoensis was 0.37, 0.70 and 0.55
respectively. Parasitologically, mean parasite rates of 26.67%, 15.05% and
23.85% were, respectively, recorded from children living under the above
conditions stated for passive experiment. Similarly, the mean spleen rates of
50.0%, 26.9%, and 47.37% were recorded, respectively. CONCLUSION: These
observations in the present study indicate that the presence of cattle in
homesteads tends to increase the man biting rate of An. arabiensis, although
differences in the mean HBR of vector mosquitoes were not statistically
significant for all groups. In contrast, cattle keeping in separate cattle sheds
outside of the human dwellings tends to reduce the man biting rate of An.
arabiensis and malaria transmission in the study area.
PMID: 12625690
East Afr Med J  2002 Sep;79(9):480-4 
Molecular markers in epidemiological monitoring of the spread of resistance
to antimalarials: a review.
Nyamwange CI, Nyamogoba H.
Department of Medical Microbiology and Parasitology, Faculty of Health Sciences,
Moi University, P.O. Box 4606, Eldoret, Kenya.
OBJECTIVE: To review the prevalence and distribution of resistance to
chloroquine and pyrimethamine-sulphadoxine combination and the use of molecular
markers for monitoring the spread of the resistance. DATA SOURCES: Literature
search on compact disk-read only memory (CD-ROM), Medline and Internet, using
the key words: Malaria and epidemiology, malaria and resistance,
sulphadoxine-pyrimethamine resistance and chloroquine resistance. Some articles
were manually reviewed. STUDY SELECTION: Relevant studies or articles on
resistance to chloroquine, sulphadoxine pyrimethamine combination and other
antimalarials and molecular resistance markers from various sources are included
in the review. DATA EXTRACTION: From individual study or articles. DATA
SYNTHESIS: Information on antimalarial resistance is harmonised under the
headings; Introduction, Prevalence and distribution of resistance to
antimalarials, Use of molecular markers for epidemiological monitoring of
antimalarial resistance. CONCLUSION: The spread and status of resistance to
sulphadoxine-pyrimethamine (SP) and chloroquine should be monitored constantly
in major health facilities. This will not only detect the emergence of
resistance to these drugs but also generate information on the extent of
resistance to these antimalarials. Mutations in the dhfr and dhps genes can be
used as markers in SP resistance surveilance while the presence of pfcrt
mutations thought to confer resistance should also be analysed to ascertain
whether they truly correlate to the resistance patterns that have been observed
in various malarious regions. Little is known on the interaction and exact
role(s) of PfCRT protein in conferring the resistance trait.
PMID: 12625689 [PubMed - in process]
Trans R Soc Trop Med Hyg  2002 Nov-Dec;96(6):683-4 
Comparison of tafenoquine (WR238605) and primaquine in the post-exposure
(terminal) prophylaxis of vivax malaria in Australian Defence Force personnel.
Nasveld P, Kitchener S, Edstein M, Rieckmann K.
Australian Defence Force Combined Health Element, Loloho, North Solomons
Province, Papua New Guinea.
On return from duty in North Solomons Province (including Bougainville Island),
Papua New Guinea, 586 Australian Defence Force personnel received either
primaquine (14-d) or tafenoquine (3-d) post-exposure malaria prophylaxis. Within
12 months, 6 of the 214 volunteers receiving primaquine and 7 of 378 receiving
tafenoquine had developed vivax malaria. Overall, volunteers preferred the
shorter course of tafenoquine. PMID: 12625150
Trans R Soc Trop Med Hyg  2002 Nov-Dec;96(6):670-3 
Efficacy of amodiaquine for uncomplicated Plasmodium falciparum malaria
in Harper, Liberia.
Checchi F, Balkan S, Vonhm BT, Massaquoi M, Biberson P, Eldin de Pecoulas P,
Brasseur P, Guthmann JP.
Malaria Control Program, Ministry of Health and Social Welfare, Monrovia,
In the face of spreading chloroquine and sulfadoxine-pyrimethamine (SP)
resistance, amodiaquine remains a cheap and efficacious alternative for treating
uncomplicated Plasmodium falciparum malaria in many settings. In Harper,
south-eastern Liberia, a previous study we conducted showed very high levels of
resistance to both chloroquine and SP. In 2001, in an effort to look for
possible alternatives, we measured in the same setting the efficacy of
amodiaquine in a 28-d study in vivo, with results corrected by polymerase chain
reaction genotyping to distinguish recrudescences from reinfections. In total,
107 children were included in the study and received a 3-d supervised course of
25 mg/kg amodiaquine. Of these, 81 were analysable at day 28. The overall
failure rate was 19.8% (95% CI 11.7-30.1%) considering both parasitological and
clinical outcomes. These results provide hitherto missing data on amodiaquine in
Liberia, and confirm that the drug may still be efficacious in settings where
chloroquine and SP are failing. We recommend the introduction of amodiaquine in
association with artesunate as a first-line antimalarial in Harper.
PMID: 12625148 [PubMed - in process]
Trans R Soc Trop Med Hyg  2002 Nov-Dec;96(6):664-9 
High Plasmodium falciparum resistance to chloroquine and
sulfadoxine-pyrimethamine in Harper, Liberia: results in vivo and
analysis of point mutations.
Checchi F, Durand R, Balkan S, Vonhm BT, Kollie JZ, Biberson P, Baron E, Le Bras
J, Guthmann JP.
Laboratoire de Parasitologie-Mycologie, Hopital Bichat-Claude Bernard, 46 rue
Henri Huchard, 75877 Paris, France.
In Liberia, little information is available on the efficacy of antimalarials
against Plasmodium falciparum malaria. We measured parasitological resistance to
chloroquine and sulfadoxine-pyrimethamine (SP) in Harper, south-west Liberia in
a 28-d study in vivo. A total of 50 patients completed follow-up in the
chloroquine group, and 66 in the SP group. The chloroquine failure rate was
74.0% (95% confidence interval [95% CI] 59.7-85.4%) after 14 d of follow-up and
84.0% (95% CI 70.9-92.8%) after 28 d (no polymerase chain reaction [PCR]
analysis was performed to detect reinfections in this group). In the SP group,
the failure rate was 48.5% (95% CI 36.2-61.0%) after 14 d and 69.7% (95% CI
57.1-80.4%) after 28 d, readjusted to 51.5% (95% CI 38.9-64.0%) after taking
into account reinfections detected by PCR. Genomic analysis of parasite isolates
was also performed to look for point mutations associated with resistance.
Genotyping of parasite isolates revealed that all carried chloroquine-resistant
K-76T mutations at gene pfcrt, whereas the triple mutation (S108N, N511, C59R)
at dhfr and the A437G mutation at dhps, both associated with resistance to SP,
were present in 84% and 79% of pretreatment isolates respectively. These results
seriously question the continued use of chloroquine and SP in Harper and
highlight the urgency of making alternative antimalarial therapies available.
Our study confirms that resistance to chloroquine may be high in Liberia and
yields hitherto missing information on SP. 
PMID: 12625147 [PubMed - in process]
Trans R Soc Trop Med Hyg  2002 Nov-Dec;96(6):660-3 
Reassessment of the resistance of Plasmodium falciparum to chloroquine in
Gabon: implications for the validity of tests in vitro vs. in vivo.
Borrmann S, Binder RK, Adegnika AA, Missinou MA, Issifou S, Ramharter M,
Wernsdorfer WH, Kremsner PG.
Medical Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon.
Email: [email protected]
Increasing resistance of Plasmodium falciparum to antimalarial drugs presents a
major risk factor for people living in endemic areas of tropical Africa. In
Lambarene, Gabon, regular surveillance of chloroquine sensitivity of P.
falciparum in vitro has been carried out since 1992 using the WHO standard
microtest. Results indicated that from 1994 onwards chloroquine resistance in
vitro decreased significantly and that by 2000, about 70% of parasite isolates
seemed to be sensitive to chloroquine in vitro. In 2001, we conducted a clinical
study to reassess the efficacy of chloroquine in vivo for the treatment of
uncomplicated P. falciparum malaria. Twenty-six patients aged 4-15 years were
included in this study. Most unexpectedly, the study demonstrated high-grade
resistance to chloroquine in vivo (failure rate on day 28 of 100%). As a
consequence, tests of parasite susceptibility to chloroquine in vitro were
repeated using the same protocol except for the replacement of previously used
commercially available predosed WHO culture plates by independently dosed
plates. All tested P. falciparum isolates were highly resistant to chloroquine,
correlating well with our clinical findings. We concluded that high level
resistance of P. falciparum to chloroquine persists in the study area. Neglect
or absence of quality controls of essential test material can lead to invalid
study results and wrong conclusions and should always be suspected in the case
of major fluctuations in the sensitivity patterns of an antimalarial drug in
vitro. In addition, our results highlight the supreme value of tests in vivo in
providing reliable estimates of the efficacy of an antimalarial in a specific
area. PMID: 12625146
Trans R Soc Trop Med Hyg  2002 Nov-Dec;96(6):655-9 
A randomized, double-blind study on the efficacy and safety of a practical
three-day regimen with artesunate and mefloquine for the treatment of
uncomplicated Plasmodium falciparum malaria in Africa.
Massougbodji A, Kone M, Kinde-Gazard D, Same-Ekobo A, Cambon N, Mueller EA.
Centre National Hospitalier et Universitaire, Cownou, Benin.
A randomized, double-blind, parallel-group study in 104 hospitalized patients
with acute, uncomplicated Plasmodium falciparum malaria was performed in West
and Central Africa from March to July 2001. Patients were randomized to receive
simultaneous dosing (artesunate 200 mg/d plus mefloquine 250 mg/d from the first
to the third day [investigational group]) or sequential dosing (artesunate 200
mg/d for 3 d plus mefloquine 250 mg on the second and 500 mg on the third day
[reference group]). Patients were followed-up for 28 d, and clinical and
parasitological outcomes were assessed. The 14-d cure rate was 100% in the
investigational group and 98% in the reference group with no recrudescence until
day 28. Mean times to fever and parasite clearance were similar between the 2
groups (32 h vs. 26 h and 45 h vs. 48 h) and tolerability was good in both
groups. The number of patients with vomiting was statistically significantly
lower in the investigational group compared to the reference group (3.8% vs.
19.2%, P = 0.014). A 3-d once-daily co-administration of artesunate and
mefloquine starting on day one offers a practical dosing regimen, which is
highly effective and well tolerated in patients with uncomplicated P. falciparum
malaria. PMID: 12625145
Trans R Soc Trop Med Hyg  2002 Nov-Dec;96(6):647-8 
Case report: severe acute symptomatic hyponatraemia in falciparum malaria.
Ustianowski A, Schwab U, Pasvol G.
Department of Infection and Tropical Medicine, Faculty of Medicine, Imperial
College, Lister Unit, Northwick Park Hospital, Harrow, Middlesex HA1 3UJ, UK.
Hyponatraemia is a common finding in malaria, but rarely appears to be of
clinical significance. We describe a case of acute, profound, hyponatraemia with
confusion and convulsions developing in the context of seemingly uncomplicated
Plasmodium falciparum malaria. We draw attention to this rarely reported and
poorly documented life-threatening complication and review the limited
literature on the subject. PMID: 12625142
Trans R Soc Trop Med Hyg  2002 Nov-Dec;96(6):644-6 
Haemozoin as a marker of placental parasitization.
McGready R, Brockman A, Cho T, Levesque MA, Tkachuk AN, Meshnick SR, Nosten F.
Shoklo Malaria Research Unit, P.O. Box 46, Mae Sot 63110, Thailand.
Email: [email protected]
Both Plasmodium vivax and P. falciparum malaria can cause the delivery of low
birthweight babies. In this report, we have quantitated haemozoin levels in
placentas from women living on the Thai-Burmese border in a region of low
transmission for both P. falciparum and P. vivax malaria from June 1995 to
January 2000. P. falciparum malaria infections during pregnancy lead to the
accumulation of haemozoin (malaria pigment) in the placenta, especially in
infections near term and in primigravid pregnancies. Haemozoin concentration was
not associated with adverse birth outcomes. Women with P. vivax infections
during pregnancy do not have measurable levels of placental haemozoin suggesting
that P. vivax-infected erythrocytes do not accumulate in the placenta as much as
P. falciparum-infected ones. PMID: 12625141
Trans R Soc Trop Med Hyg  2002 Nov-Dec;96(6):620-6 
Anopheline vectors and malaria transmission in eastern Afghanistan.
Rowland M, Mohammed N, Rehman H, Hewitt S, Mendis C, Ahmad M, Kamal M, Wirtz R.
HealthNet International, Peshawar, Pakistan. 
Email: [email protected]
Anopheline vectors and malaria transmission were studied in 2 river-irrigated,
rice-growing districts of eastern Afghanistan from May 1995 to December 1996.
Clinical malaria was monitored in 12 rural villages (population 14,538) by
passive case detection at local clinics. Adult mosquitoes were collected by
space-spraying of living quarters and stables and by cattle bait catches.
Mosquito head-thoraces (17,255 specimens) were tested for Plasmodium falciparum
and P. vivax circumsporozoite protein (CSP) using enzyme-linked immunosorbent
assay. The recorded incidence of P. vivax and P. falciparum was 199 and 41
episodes per 1000 person years, respectively. Twelve species of anopheline were
recorded; Anopheles stephensi comprised 82% and A. culicifacies 5%. Eight
species tested positive for CSP: A. stephensi, A. culicifacies, A. fluviatilus,
A. annularis, A. pulcherrimus, A. maculatus, A. splendidus and A. superpictus.
Among infected mosquitoes 46% were positive for P. falciparum, 45% for P. vivax
VK-247, and 9% for P. vivax PV-210. Estimates of the feeding rates of infective
vectors on humans indicated that A. stephensi would contribute 76% of infective
bites, A. fluviatilis and A. pulcherrimus 7% each, and A. culicifacies and A.
superpictus 3% each. The overall infective vector feeding rate correlated with
the P. vivax incidence rate in the human population. The conventional view of A.
culicifacies being the main rural vector and A. stephensi important only in
urban settings needs to be reconsidered in western outreaches of the
Indo-Pakistan subcontinent. PMID: 12625136
Trans R Soc Trop Med Hyg  2002 Nov-Dec;96(6):597-9 
Mortality in a seven-and-a-half-year follow-up of a trial of insecticide-treated
mosquito nets in Ghana.
Binka FN, Hodgson A, Adjuik M, Smith T.
Navrongo Health Research Centre, P.O. Box 114, Navrongo, Ghana.
A 17% efficacy in preventing all-cause mortality in children aged 6-59 months
was previously reported from a cluster-randomized controlled trial of
insecticide-treated mosquito nets (ITNs) carried out in the Kassena-Nankana
District of northern Ghana from July 1993-June 1995. A follow-up until the end
of 2000 found no indication in any age group of increased mortality in the ITN
group after the end of the randomized intervention. These results should further
encourage the use of ITNs as a malaria control tool in areas of high endemicity
of Plasmodium falciparum. PMID: 12625130
Trans R Soc Trop Med Hyg  2002 Nov-Dec;96(6):593-6 
Zooprophylaxis, artefact or reality? A paired-cohort study of the effect of
passive zooprophylaxis on malaria in The Gambia.
Bogh C, Clarke SE, Walraven GE, Lindsay SW.
Danish Bilharziasis Laboratory, Jaegersborg Alle 1D, DK-2920 Charlottenlund,
Denmark. Email: [email protected]
The World Health Organization has recommended the use of cattle for
zooprophylaxis as a protective measure against malaria since 1982. However,
concern has been raised about this practice, since some studies have shown that
the presence of cattle may instead increase malaria prevalence. This study was
designed to investigate the effect of passive zooprophylaxis on malaria in an
area of moderate seasonal transmission in The Gambia, West Africa. The study was
based on a paired-cohort of 204 children aged < 7 years, sleeping < 20 m or > 50
m from cattle, and surveys were done from 14 October to 2 December 1997.
Entomological investigations showed that the presence of cattle did not alter
the risk of malaria transmission in nearby houses. There was also no significant
difference in the prevalence of Plasmodium falciparum between the 2 groups.
Although the presence of cattle appeared to be protective against high
parasitaemia, cattle were also associated with greater wealth of the children's
families. Conditional logistic regression analysis showed that the decreased
risk of high parasitaemia in the group with cattle present was an artefact
associated with the higher general wealth of the cattle owners. We concluded
that zooprophylaxis is not an effective intervention method against malaria in
settings similar to The Gambia. PMID: 12625129

Trans R Soc Trop Med Hyg  2002 Nov-Dec;96(6):586-92 
Risk factors for malaria in pregnancy in an urban and peri-urban population
in western Kenya.
van Eijk AM, Ayisi JG, ter Kuile FO, Misore AO, Otieno JA, Rosen DH, Kager PA,
Steketee RW, Nahlen BL.
Kenya Medical Research Institute, Centre for Vector Biology and Control
Research, Kisumu, Kenya. Email: [email protected]
To assess risk factors for malaria in pregnancy in Kisumu, western Kenya, we
studied healthy women with an uncomplicated pregnancy of > or = 32 weeks
attending the antenatal clinic in the Provincial Hospital. Between June 1996 and
March 1999, malaria and human immunodeficiency virus (HIV) infection were
examined in 5093 pregnant women: 20.1% of the women were parasitaemic and
24.9% were HIV-seropositive. 2502 women delivered in the hospital and a smear
was obtained: the prevalence of placental malaria, maternal peripheral parasitaemia,
and HIV infection was respectively 19.0%, 15.2% and 24.5%. HIV infection (risk
ratio [RR] 1.58, 95% confidence interval [95% CI] 1.32-1.89), young age (< 21
years: RR 1.51, 95% CI 1.19-1.91), being a primigravidae (RR 1.41, 95% CI
1.05-1.88), a peri-urban residence (RR 1.50, 95% CI 1.21-1.88), and Luo
ethnicity (RR 1.74, 95% CI 1.35-2.24) were risk factors for malaria at delivery.
Use of sulfadoxine-pyrimethamine (SP), reported by 2.1% of the women, was a
protective factor (RR 0.44, 95% CI 0.18-1.06). Results were similar in the third
trimester. In this urban/peri-urban setting, preventing HIV infection, delaying
the first pregnancy until after adolescence, and applying an effective
antimalarial strategy such as intermittent therapy with SP will reduce the
prevalence of malaria in pregnancy. PMID: 12625128
Clin Infect Dis  2003 Jan 15;36(Suppl 1):S4-10 
The global impact of drug resistance.
Howard DH, Scott RD 2nd, Packard R, Jones D.
Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Email: [email protected]
Measuring the impact of drug resistance is an important step in understanding
the scope of the problem and formulating policies to limit the emergence and
spread of resistant organisms. Studies have focused on measuring the increased
costs, morbidity, and mortality in patients with infections due to resistant
versus susceptible organisms. These have generally found that resistance worsens
outcomes. By focusing only on infected patients, however, they may understate
the impact of resistance. It is important to recognize that resistance also
affects the treatment of individuals with nonresistant organisms. In areas with
high rates of resistance, physicians and governments have changed empiric
therapy for malaria, tuberculosis, acute respiratory infections, and other
diseases, increasing overall treatment costs. In some instances, these costs may
exceed those attributable to treatment failure. PMID: 12516025