Social Sciences and Malaria Control

Health Policy and Planning 2002, 17/4 (402-411)

Willingness to pay for treated mosquito nets in Surat, India: The design

and descriptive analysis of a household survey

Bhatia M.R.; Fox-Rushby J.A.

Department of Social Policy, London School of Economics,

Houghton Street, London, WC2A 2AE  United Kingdom

Email: [email protected]

For willingness to pay (WTP) studies to have an appropriate impact on

policy making, it is essential that the design and analysis are undertaken carefully. This

paper aims to describe and justify the design of the survey tool used to assess hypothetical

WTP for treated mosquito nets (TMN) in rural Surat, India and report its findings. Results from

qualitative work were used as an input for developing the WTP questionnaire. A total of 1200

households belonging to 80 villages in rural Surat were selected for the study. A bidding

format was used to elicit WTP values, using three different starting bids. The scenario was

constructed in a way to reduce the possibility of respondents acting strategically.

The response rate was 100%. About 79% of the respondents were willing to buy TMNs

and the mean WTP was Rs57. Descriptive results of economic and other taste and preference

 variables are also presented, which include preventive measures used by households and

treatment seeking behaviour for malaria. It is observed that WTP as well as demographic variables

and prevention methods differ significantly across arms of the trial. This paper suggests that

policy-makers could use the evidence following further analysis, along with information on costs

of implementation, to ascertain the levels of subsidy that may be needed at different levels of coverage.

Health Policy and Planning 2002, 17/4 (333-344)

Self-treatment for malaria: The evidence and methodological issues

McCombie S.C.

Department of Anthropology, Georgia State University, 33

Gilmer Street, Atlanta, GA 30303-3083  United States

Email: [email protected]

Malaria remains an important cause of death, especially in sub-Saharan

Africa. Self-treatment with antimalarial drugs is a common practice  that raises important

issues for policy-makers. A number of important questions concerning factors related to

self-treatment, adequacy of self-treatment and the role of self-treatment in malaria mortality

remain unanswered. Although there are some common patterns, there is considerable diversity

in treatment practices, even within a single country. Social science research on malaria treatment

needs to move beyond description to evaluation of interventions. This will require a greater degree

of methodological rigour and more attention to the generation of data that can be compared across

time periods and studies. Definitions of malaria cases and the role of local disease categories in

identifying cases need to be made more explicit. Illnesses should be classified by severity,

using measures of perceived severity as well as biomedical signs of severity. Each treatment step

should be considered in terms of four levels of analysis: who provided the treatment or advice,

what the treatment was, where it was obtained and when it was taken in relationship to onset of illness. 

Social Science & Medicine.  55(12):2215-26, 2002 Dec.

Strategies to improve adherence to recommended chloroquine treatment

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

care delivery in Ghana.

Agyepong IA. Ansah E. Gyapong M. Adjei S. Barnish G. Evans D.

District Health Administration, PO Box 1, Dodowa, Ghana.

Email: [email protected]

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.

Social Science & Medicine.  55(12):2121-30, 2002 Dec.

Investigating starting-point bias: a survey of willingness to pay for

insecticide-treated nets.

Onwujekwe O.  Nwagbo D.

Health Policy Research Unit, Department of Pharmacology and Therapeutics, College of Medicine,

University of Nigeria, Enugu-Campus, Nigeria.
Email: [email protected]

The objective of this study was to investigate the existence of

starting-point bias in the bidding game contingent valuation elicitation technique when determining

 the willingness to pay (WTP) for insecticide-treated nets (ITNs) and ITNs re-treatment in rural Nigeria.

Of all existing contingent techniques, the bidding game most closely mimics the normal price taking

behaviour in local markets in Nigeria. Three different starting-points (low, medium and high) were used

to determine WTP for large and small ITNs, and for ITNs re-treatment, respectively. The respondents

were randomly assigned to any of the starting-points and a pre-tested interviewer-administered questionnaire

used to elicit WTP. Non-parametric tests and the Tobit model were used to analyse the data for evidence of

starting-point bias. Plots of respondents’ cumulative density functions by starting-points were also examined to

show the pattern of responses. The non-parametric tests showed no statistically significant differences between

the three starting points in WTP for large ITNs (p =0.262) and for ITNs re-treatment (p = 0.412). However, there

was a statistical significant difference in WTP for small ITNs (p = 0.045). Nevertheless, in this instance, the high

starting point group had a lower mean WTP than the low group, and also had the lowest median WTP amongst the

three groups. However, using the conditional WTP (only males), there were no differences among the three starting-points for all goods. The multiple regression analyses using the Tobit model confirmed the results of the non-parametric tests. The plots of cumulative densities were also similar for the three starting-points for the three products. However, the high starting-point group had those more willing to pay higher amounts for large and small nets. There was no conclusive evidence of starting-point bias. Future research is required in order to gain a deeper understanding on factors determining peoples’ valuation of goods and services, reasons for any type of starting-point bias, and how the bidding game can be improved.

                                       PubMed

Am J Epidemiol  2003 Feb 1;157(3):203-9 

Maternally Transmitted Antibodies to Pregnancy-Associated Variant Antigens on the Surface of Erythrocytes Infected with Plasmodium falciparum: Relation to Child Susceptibility to Malaria.

Cot M, Le Hesran JY, Staalsoe T, Fievet N, Hviid L, Deloron P.

Mother and Child Health in the Tropics, Research Institute for Development

(IRD), Hopital Tenon, Paris, France.

The consequences of pregnancy-associated malaria on a child's health have been

poorly investigated. Malarial infection of the placenta seems to result in a

higher susceptibility of children to the parasite during their first year of

life. In 1993-1995, the authors investigated the role of antibodies in variable

surface antigens (VSA) specific to chondroitin sulfate A (CSA)-binding parasites

to assess the parasitologic status of the child. Flow cytometry was used to

measure levels of antibodies to VSA from CSA-selected and -unselected parasite

lines in the cord blood of 79 newborns in Ebolowa, Cameroon. These newborns were

subsequently followed up for 2 years to determine the date of first occurrence

of blood parasites and mean parasite density during follow-up. Maternally

transmitted antibodies to VSA expressed by CSA-binding parasites, but not

antibodies to any other specificity, were negatively related to time of first

appearance of Plasmodium falciparum in a child's blood and were positively

related to mean parasite density during the first 2 years of life. If maternal

infection is thought to be the main mechanism influencing susceptibility of the

newborn to malaria, antibodies to VSA may better denote maternal malaria

infection during almost the entire pregnancy as opposed to placental blood smear

reflecting infection during the last few months of pregnancy.

Parasitol Int  2003 Mar;52(1):81-93 

A mathematical model for the transmission of Plasmodium vivax malaria.

Ishikawa H, Ishii A, Nagai N, Ohmae H, Harada M, Suguri S, Leafasia J.

Department of Environmental and Mathematical Sciences, Faculty of Environmental

Science and Technology, Okayama University, Tsushimanaka, 700-8530, Okayama,

Japan

We have proposed a mathematical model for the transmission of Plasmodium vivax

malaria quantitatively, which is adjusted to the infected region, Guadalcanal,

in the Solomon Islands. The simulation of a transmission model will be

instrumental in planning the malaria control strategy. A characteristic of the

life cycle of P. vivax is that a sporozoite injected into the blood stream by a

mosquito bite may sometimes stay in a hepatocyte as a hypnozoite. Therefore, we

have incorporated a phenomenon of renewed infections caused by a relapse into

the transmission model. Also through the simulations we have attempted to

evaluate the decline in prevalence caused by the programs of selective mass drug

administration (MDA) and vector control such as the distribution of

permethrin-treated bednets. The simulations have indicated that the concentrated

repetition of MDA at 1-week intervals would reduce the prevalence of vivax

malaria swiftly in the beginning and would keep the parasite rate below 1% for a

few years but the prevalence would increase thereafter. In contrast, the

parasite rate would remain below 1% for a long time if a trial of 1 or 2 times

MDA is accompanied with some reduction of the vectorial capacity by the

enforcement of vector control. In any case, it is important to beware of relapse

cases because even after the execution of MDA it takes a long time to decrease

the proportion of hypnozoite carriers.

Parasitol Int  2003 Mar;52(1):61-70 

Expansion of unconventional T cells with natural killer markers in malaria

patients.

Watanabe H, Weerasinghe A, Miyaji C, Sekikawa H, Toyabe S, Mannor MK, Morshed

SR, Halder RC, Kobayashi J, Toma H, Sato Y, Iwai K, Matsuoka H, Abo T.

Department of Immunology, Niigata University School of Medicine, 951-8510,

Niigata, Japan

Immunological states during human malarial infection were examined. In parallel

with parasitemia and anemia, granulocytosis was induced in the blood of

patients, especially those infected with Plasmodium (P.) falciparum. At that

time, the level of lymphocytes remained unchanged or slightly increased in the

blood. However, the distribution of lymphocyte subsets was modulated, showing

that the proportion of CD56(+)T cells, CD57(+)T cells, and gammadeltaT cells

(i.e. all unconventional T cells) had increased in patients infected with P.

falciparum or P. vivax. This phenomenon occurred at the early phase of infection

and disappeared in the course of recovery. The data from patients with multiple

attacks of P. vivax infection showed that there was no augmentation of these

responses. In adult cases, the increase in the proportion of unconventional T

cells seemed to closely parallel disease severity. However, all these responses

were weak in children, even those infected with P. falciparum. In conjunction

with accumulating evidence from mouse malaria experiments, the present results

suggest that the immunological state induced by malarial infection might mainly

be an event of unconventional T cells and that the immunological memory might

not be long-lasting, possibly due to the properties of unconventional T cells.

Parasitol Int  2003 Mar;52(1):53-9 

Oral artesunate prevents Plasmodium berghei Anka infection in mice.

Gumede B, Folb P, Ryffel B.

Department of Pharmacology, University of, Cape Town, South Africa

Artesunate, a semi-synthetic derivative of a naturally occurring anti-malarial

artemisinin was compared with chloroquine in C57BL/6 mice infected with

Plasmodium berghei Anka (PbA). A 7-day oral administration of artesunate

prevented parasitaemia at 10 mg/kg/day. However, recrudescence of parasitaemia

and cerebral malaria occurred upon cessation of treatment followed by death

within 28 days. However, a 14-day course of artesunate (100 mg/kg/day) prevented

completely the development of parasitaemia and cerebral malaria with a survival

of more than 60-days as did 10 mg/kg/day chloroquine. These data demonstrate

that oral artesunate inhibits PbA and prevents cerebral malaria, but needs to be

administered at high dose and for prolonged time to eradicate PbA infection in

mice.

Parasitol Int  2003 Mar;52(1):41-52 

Characterisation of a sexual stage-specific gene encoding ORC1 homologue in the human malaria parasite Plasmodium falciparum.

Li JL, Cox LS.

Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU,

Oxford, UK

The origin recognition complex (ORC) is a multisubunit protein composed of six

polypeptides that binds to replication origins and is essential for the

initiation of chromosomal DNA replication. Using the Vectorette technique, we

have isolated a novel gene encoding an ORC1-like protein from the human malaria

parasite Plasmodium falciparum. The gene has no introns and encodes a protein

(PfORC1) of 1189 amino acid residues with a predicted molecular mass of 139 kDa.

PfORC1 contains all conserved sequences in the ORC1/Cdc6/Cdc18 family and

displays the highest homology to the Schizosaccharomyces pombe ORC1. However,

PfORC1 possesses an extensive N-terminal segment with several interesting

features including multiple potential phosphorylation sites, a large proportion

of charged amino acids, four copies of a heptamer repeat, two nuclear

localisation signals, and a leucine zipper motif. Southern blot analyses show

that the Pforc1 gene is present as a single copy per haploid genome and is

located on chromosome 12. A 5600 nucleotide transcript of this gene is expressed

predominantly in the sexual erythrocytic stage, indicating that PfORC1 may be

involved in gametogenesis during which DNA is quickly replicated.

Parasitol Int  2003 Mar;52(1):1-11 

Transmission-blocking vaccine of vivax malaria.

Tsuboi T, Tachibana M, Kaneko O, Torii M.

Department of Molecular Parasitology, Ehime University School of Medicine,

Shigenobu-cho, 791-0295, Ehime, Japan

Malaria remains one of the leading causes of both morbidity and mortality of

humans residing in tropical countries. For many malarious regions outside of

Africa, development of effective transmission-blocking vaccines will require

coverage against both Plasmodium falciparum and Plasmodium vivax. The genes

coding for two potential P. vivax transmission-blocking antigens, Pvs25 and

Pvs28, have been cloned. Mice vaccinated with yeast-produced recombinant

proteins Pvs25 and Pvs28 adsorbed to aluminum hydroxide developed strong

antibody responses against the immunogens. The development of oocysts in

mosquitoes was completely inhibited when these antisera were ingested with the

P. vivax Salvador (Sal) I strain-infected chimpanzee blood. In a large

collection of P. vivax field isolates, we found only 5 nucleotide changes that

would result in amino acid substitutions in Pvs25. In contrast, the Pvs28 gene

had 22 nucleotide changes that would result in conservative amino acid

substitutions. How the antigenic polymorphism of Pvs25 and Pvs28 would affect

the efficacy of Sal I based vaccine remains to be elucidated. Clinical trials

with Pvs25 and the P. falciparum ortholog Pfs25 are in preparation.

Cell Microbiol  2003 Jan;5(1):3-14 

Insect immunity and its implication in mosquito-malaria interactions.

Dimopoulos G.

Centre for Molecular Microbiology and Infection, Department of Biological

Sciences, Imperial College of Science, Technology and Medicine, SW7 2AZ London,

UK.

Insects' resistance to infectious agents is essential for their own survival and

also for the health of the plant, animal and human populations with which they

closely interact. Several of the major human diseases are spread by insects and

are rapidly expanding as a result of the development of insecticide resistance

in vectors and drug resistance in parasites. A vector insects' permissiveness to

a pathogen, and hence the spread of the disease, will largely depend on the

compatibility of the molecular interactions between the two species and the

capability of the insect immune system to recognize and kill the pathogen. The

innate immune system comprises a variety of components and mechanisms that can

discriminate between different microorganisms and mount specific responses to

control pathogenic infections. An impressive body of knowledge on the insects'

innate immunity has been generated from studies in the model organism

Drosophila. These studies are now guiding the exploration of the immune system

in the vector mosquito of human malaria, Anopheles, and its implication in the

elimination of parasites. Anopheles immune responses have been linked to

parasite losses and some refractory mosquitoes can kill all parasites through

specific defence mechanisms. The recently sequenced Drosophila and Anopheles

genomes provide a detailed and comparative view on their immune gene repertoires

that in combination with post-genomic analyses is used to further dissect the

complex mechanisms of Plasmodium killing in the mosquito.

J Am Mosq Control Assoc  2002 Dec;18(4):359-63 

Colonization of Anopheles maculatus from Central Java, Indonesia.

Bangs MJ, Soelarto T, Barodji, Wicaksana BP, Boewono DT.

US Naval Medical Research Unit No. 2, Kompleks P2M/LitBangKes, Jl. Percertakan

Negara No. 29, Jakarta, 10560 Indonesia.

The routine colonization of Anopheles maculatus, a reputed malaria vector from

Central Java, is described. The strain is free mating and long lived in the

laboratory. This species will readily bloodfeed on small rodents and artificial

membrane systems. Either natural or controlled temperatures, humidity, and

lighting provide acceptable conditions for continuous rearing. A simple larval

diet incorporating a 10:4 powdered mixture of dried beef and rice hulls proved

acceptable. Using a variety of simple tools and procedures, this colony strain

appears readily adaptable to rearing under most laboratory conditions. This

appears to be the first report of continuous colonization using a free-mating

strain of An. maculatus. Using this simple, relatively inexpensive method of

mass colonization adds to the short list of acceptable laboratory populations

used in the routine production of human-infecting plasmodia.

J Am Mosq Control Assoc  2002 Dec;18(4):329-40 

The potential of intermittent irrigation for increasing rice yields, lowering

water consumption, reducing methane emissions, and controlling malaria in

African rice fields.

Keiser J, Utzinger J, Singer BH.

Office of Population Research, Princeton University, Princeton, NJ 08544, USA.

Rice production in sub-Saharan Africa has more than doubled in the last 3

decades and the potential to further develop rice-harvested areas is

considerable. Several studies have demonstrated that the transformation of

arable land into rice irrigation might create suitable habitats for large

populations of disease vectors. Prominent among those are anopheline mosquitoes

responsible for transmission of malaria. The method of irrigation on an

intermittent basis during the rice-cropping calendar has gained renewed interest

as a potentially effective malaria control strategy since the early 1980s. We

review the experiences of the past 80 years with intermittent irrigation in the

cultivation of rice. This method has been shown to reduce significantly the

density of malaria vectors by curtailing their larval development. Furthermore,

reduced methane emissions and water savings with at least equal yields were

achieved in intermittently irrigated rice fields. We explore and discuss under

what conditions intermittent irrigation might be beneficial in new rice-growing

areas and identify steps that have to be taken to expand such programs in the

future.

Malar J  2002 Dec 18;1(1):19 [epub ahead of print] 

MalariaSphere: A greenhouse-enclosed simulation of a natural Anopheles

gambiae (Diptera: Culicidae) ecosystem in western Kenya.

Knols BG, Njiru BN, Mathenge EM, Mukabana WR, Beier JC, Killeen GF.

International Centre of Insect Physiology and Ecology (ICIPE), Mbita Point

Research & Training Centre, PO Box 30, Mbita Point, Kenya. 

Email: [email protected]

BACKGROUND: The development and implementation of innovative vector control

strategies for malaria control in Africa requires in-depth ecological studies in

contained semi-field environments. This particularly applies to the development

and release of genetically-engineered vectors that are refractory to Plasmodium

infection. Here we describe a modified greenhouse, designed to simulate a

natural Anopheles gambiae Giles ecosystem, and the first successful trials to

complete the life-cycle of this mosquito vector therein. METHODS: We constructed

a local house, planted crops and created breeding sites to simulate the natural

ecosystem of this vector in a screen-walled greenhouse, exposed to ambient

climate conditions, in western Kenya. Using three different starting points for

release (blood-fed females, virgin females and males, or eggs), we allowed

subsequent stages of the life-cycle to proceed under close observation until one

cycle was completed. RESULTS: Completion of the life-cycle was observed in all

three trials, indicating that the major life-history behaviours (mating, sugar

feeding, oviposition and host seeking) occurred successfully. CONCLUSION: The

system described can be used to study the behavioural ecology of

laboratory-reared and wild mosquitoes, and lends itself to contained studies on

the stability of transgenes, fitness effects and phenotypic characteristics of

genetically-engineered disease vectors. The extension of this approach, to

enable continuous maintenance of successive and overlapping insect generations,

should be prioritised. Semi-field systems represent a promising means to

significantly enhance our understanding of the behavioural and evolutionary

ecology of African malaria vectors and our ability to develop and evaluate

innovative control strategies. With regard to genetically-modified mosquitoes,

development of such systems is an essential prerequisite to full field releases.

Int J Health Geogr  2002 Dec 9;1(1):4 [epub ahead of print] 

The application of geographical information systems to important public health problems in Africa.

Tanser FC, Le Sueur D.

The National Malaria Programme, Medical Research Council, PO Box 70380, Overport

4067, Durban, South Africa. 

Email: [email protected]

Africa is generally held to be in crisis, and the quality of life for the

majority of the continent's inhabitants has been declining in both relative and

absolute terms. In addition, the majority of the world's disease burden is

realised in Africa. Geographical information systems (GIS) technology,

therefore, is a tool of great inherent potential for health research and

management in Africa. The spatial modelling capacity offered by GIS is directly

applicable to understanding the spatial variation of disease, and its

relationship to environmental factors and the health care system. Whilst there

have been numerous critiques of the application of GIS technology to developed

world health problems it has been less clear whether the technology is both

applicable and sustainable in an African setting. If the potential for GIS to

contribute to health research and planning in Africa is to be properly evaluated

then the technology must be applicable to the most pressing health problems in

the continent. We briefly outline the work undertaken in HIV, malaria and

tuberculosis (diseases of significant public health impact and contrasting modes

of transmission), outline GIS trends relevant to Africa and describe some of the

obstacles to the sustainable implementation of GIS. We discuss types of viable

GIS applications and conclude with a discussion of the types of African health

problems of particular relevance to the application of GIS.

Cochrane Database Syst Rev  2003;(1):CD000169 

Drugs for preventing malaria-related illness in pregnant women and death

in the newborn (Cochrane Review).

Garner P, Gulmezoglu AM.

International Health Research Group, Liverpool School of Tropical Medicine,

Pembroke Place, Liverpool, UK, L3 5QA. 

Email: [email protected]

BACKGROUND: Malaria contributes to maternal illness and anaemia in pregnancy,

especially in first-time mothers, and could harm the mother and the baby.

Interventions to prevent or mitigate the effects of malaria during pregnancy are

often recommended. OBJECTIVES: To assess drugs given to prevent malaria

infection and its consequences in pregnant women living in malarial areas.

SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials

register (July 2002); the Cochrane Controlled Trials Register (Issue 3, 2002);

MEDLINE (1966-July 2002); EMBASE (1974-July 2002); and LILACS (accessed July

2002). We contacted researchers in the field. SELECTION CRITERIA: Randomised 

and quasi-randomised trials in pregnant women of drugs given regularly that aim to

mitigate the effects of malaria in pregnancy. DATA COLLECTION AND ANALYSIS:

Trial quality was assessed. Data extraction was done by two reviewers using

standard criteria. MAIN RESULTS: 14 trials included (n=3454); only 2 were

adequately concealed. For women of all parity groups, the meta-analysis (n=2890)

showed lower parasitaemia and placental malaria in the intervention arm. For

women having the first or second baby, there were 9 studies (n=3454). Severe

antenatal anaemia was less common (RR 0.62, 95%CI 0.50 to 0.78, 4 studies),

perinatal mortality appeared lower (RR 0.73, 95% CI 0.73 to 0.99, 3 studies).

Maternal parasitaemia was lower with the intervention (RR 0.24, 95%CI 0.14 to

0.42, random effects model, 6 studies), and mean birthweight higher (WMD 122 g,

95%I 81 to 164 g, 8 studies), and low birthweight was less common (RR 0.49,

95%CI 0.36 to 0.65, 6 studies). REVIEWER'S CONCLUSIONS: Drugs given routinely

for malaria during pregnancy reduce severe antenatal anaemia in the mother, and

are associated with higher birthweight and probably reduced perinatal mortality.

This effect appears to be limited to low parity women.

Cochrane Database Syst Rev  2003;(1):CD000129 

Vaccines for preventing malaria (Cochrane Review).

Graves P, Gelband H.

1400 W. Oak Street, Fort Collins, USA, CO 80521. 

Email [email protected] or [email protected]

BACKGROUND: Four types of malaria vaccine, SPf66 and MSP/RESA vaccines

(against the asexual stages of the Plasmodium parasite) and CS-NANP and 

RTS,S vaccines (against the sporozoite stages), have been tested in randomized

Controlled trials in endemic areas. OBJECTIVES: To assess malaria vaccines against

Plasmodium falciparum, P. vivax, P. malariae and P ovale in preventing

infection, disease and death. SEARCH STRATEGY: We searched the Cochrane

Infectious Diseases Group trials register (July 2002), the Cochrane Controlled

Trials Register (The Cochrane Library Issue 2, 2002), MEDLINE (1966 to July

2002), EMBASE (1980 to May 2002), Science Citation Index (1981 to July 2002),

and reference lists of articles. We also contacted organizations and researchers

in the field. SELECTION CRITERIA: Randomized controlled trials comparing

vaccines against Plasmodium falciparum, P. vivax, P. malariae or P. ovale with

placebo or routine antimalarial control measures in people of any age receiving

a challenge malaria infection. DATA COLLECTION AND ANALYSIS: Two reviewers

independently assessed trial quality and extracted data. MAIN RESULTS: Eighteen

efficacy trials involving 10,971 participants were included. There were ten

trials of SPf66 vaccine, four trials of CS-NANP vaccines, two trials of RTS,S

vaccine, and two of MSP/RESA vaccine. Results with SPf66 in reducing new malaria

infections (P. falciparum) were heterogeneous: it was not effective in four

African trials (Peto odds ratio (OR) 0.96, 95% confidence interval (CI) 0.81 to

1.14), but in five trials outside Africa the number of first attacks was reduced

(Peto OR 0.77, 95% CI 0.67 to 0.88). Trials to date have not indicated any

serious adverse events with SPf66 vaccine. In three trials of CS-NANP vaccines,

there was no evidence for protection by these vaccines against P. falciparum

malaria (Peto OR 1.12, 95% CI 0.64 to 1.93). In a small trial in non-immune

adults in the USA, RTS,S gave strong protection against experimental infection

with P. falciparum. In a trial in an endemic area of the Gambia in semi-immune

people, there was a reduction in clinical malaria episodes in the second year of

follow up, corresponding to a vaccine efficacy of 66% (CI 14% to 85%). In a

trial in Papua New Guinea, MSP/RESA had no protective effect against episodes of

clinical malaria. There was evidence of an effect on parasite density, but this

differed according to whether the participants had been pretreated with

sulfadoxine/pyrimethamine or not. The prevalence of infections with the parasite

subtype of MSP2 in the vaccine was reduced compared with the other subtype (Peto

OR 0.35, CI 0.23 to 0.53). REVIEWER'S CONCLUSIONS: There is no evidence for

protection by SPf66 vaccines against P. falciparum in Africa. There is a modest

reduction in attacks of P. falciparum malaria following vaccination with SPf66

in other regions. Further research with SPf66 vaccines in South America or with

new formulations of SPf66 may be justified. There was not enough evidence to

evaluate the use of CS-NANP vaccines. The RTS,S vaccine showed promising result,

as did the MSP/RESA vaccine, but it should include the other main allelic form

of MSP2. The MSP/RESA trial demonstrated that chemotherapy during a vaccine

trial may reduce vaccine efficacy, and trials should consider very carefully

whether this practice is justified.

Trop Med Int Health  2003 Jan;8(1):48-55 

Malaria control in complex emergencies: the example of East Timor.

Kolaczinski J, Webster J.

Disease Control and Vector Biology Unit, London School of Hygiene and Tropical

Medicine, London, UK Ministry of Health, Dili, East Timor HealthNet

International, Dili, East Timor.

Malaria control in complex emergencies forms part of the World Health

Organization's Roll Back Malaria (RBM) initiative. The underlying principle is a

partnership with other UN agencies and non-governmental organizations, with the

RBM programme providing support to its implementing partners through a Technical

Support Network. This innovative approach was applied for the first time in

1999-2000, following the return of stability and security to East Timor. The RBM

programme assessed the malaria situation during the acute emergency phase and

identified programme priorities. Two non-governmental organizations were

subsequently invited to operate as implementing partners. Individual proposals

were developed and funding obtained, but no overall organizational and planning

framework was established. Implementation commenced quickly, addressing aspects

of prevention, diagnosis and treatment. As East Timor progressed into the

transitional phase towards independence, the programme was not realigned to the

changing context. Absence of monitoring and evaluation was a significant factor

contributing to the resulting continuation of emergency malaria control

activities well into the transitional phase. East Timor's example of malaria

control in complex emergencies provides important lessons: (i) partnership roles

and responsibilities should be clearly defined from the beginning of the

programme, (ii) planning, monitoring and evaluation should be instigated from

the start with the aim to develop long-term strategies and policies, (iii)

expert support is necessary to guide implementation at all stages, (iv) the

flexibility to react to changing priorities should be ensured as the context of

the emergency and the available health structure changes, and (v) the

implementation process, and alternatives for continuation of activities once the

RBM complex emergency partnership has terminated, should be clarified to all

partners involved.

Trop Med Int Health  2003 Jan;8(1):37-47 

Efficacy and efficiency of new Bacillus thuringiensis var. israelensis and

Bacillus sphaericus formulations against Afrotropical anophelines in Western Kenya.

Fillinger U, Knols BG, Becker N.

International Centre of Insect Physiology and Ecology (ICIPE), Mbita Point,

Kenya Laboratory of Entomology, Wageningen University Research Centre,

Wageningen, The Netherlands German Mosquito Control Association (KABS), Waldsee, Germany.

We evaluated the efficacy of new water-dispersible granular (WDG) formulations

of Bacillus thuringienis var. israelensis (Bti; VectoBac(R)) and B. sphaericus

(Bs; VectoLex(R), Valent BioScience Corp., Illinois, USA) for the control of

larval Anopheles gambiae sensu lato Giles mosquitoes in a malaria-endemic area

around Lake Victoria, Western Kenya. WDG and powder formulations were compared

in laboratory bioassays and followed by efficiency and residual effect

assessments of both WDG formulations in open field experiments. LC50 and LC95

values for the Bti/Bs strains and their formulations show high susceptibility of

A. gambiae sensu stricto under laboratory conditions. The larvae proved more

susceptible to Bs than to Bti and the WDG formulations were slightly superior to

the powder formulations. High efficiency was also shown in the open field

trials, and a minimum dosage of 200 g/ha Bti WDG, representing the LC95 of the

laboratory tests, was sufficient to fully suppress emergence of mosquitoes when

applied at weekly intervals. Bti WDG did not show a residual effect,

irrespective of the concentration applied. The Bs WDG formulation, however,

showed significant larval reductions up to 11 days post-treatment at application

doses of either 1 or 5 kg/ha. We conclude that the main malaria vector in our

study area is highly susceptible to these microbial control agents. Minimum

effective dosages to achieve elimination of the larval population in a given

habitat are extremely low and environmental impact is negligible. Microbial

products for larval control have therefore great potential within Integrated

Vector Management programmes and may augment control efforts against adult

vector stages, such as the use of insecticide-treated bednets, in many parts of

Africa.

Trop Med Int Health  2003 Jan;8(1):30-32 

Myocardial damage in falciparum malaria detectable by cardiac troponin T is

rare.

Gunther A, Grobusch MP, Slevogt H, Abel W, Burchard GD.

Institut fur Tropenmedizin, Charite, Humboldt-Universitat zu Berlin, Germany

Institut fur Tropenmedizin, Eberhard-Karls-Universitat, Tubingen, Germany

Medizinische Klinik mit Schwerpunkt Infektiologie, Charite Campus Virchow,

Humbold-Universitat zu Berlin, Germany Abteilung fur Laboratoriumsmedizin am

Unfallkrankenhaus Berlin, Germany.

OBJECTIVES: To estimate the prevalence of myocardial damage in falciparum

malaria by serum concentration of cardiac troponin T. METHODS: Retrospective

study of stored sera and patient files; assessment of acute myocardial damage by

serum concentration or activity of cardiac troponin T, creatine kinase, creatine

kinase MB and myoglobin and by routine electrocardiography. RESULTS: A total of

161 patients with falciparum malaria were included in the study; troponin T was

elevated in one case (0.6%), no CK-MB elevations were found, myoglobin was

elevated in 10 of 161 patients (6.2%), all of whom were elderly and had

concomitant elevated serum concentration levels of cystatin C; ECG abnormalities

were seen in 23 patients. CONCLUSION: Assessed by troponin T, myocardial damage

in falciparum malaria is rare.

Trop Med Int Health  2003 Jan;8(1):19-24 

Therapeutic efficacy of chloroquine plus sulphadoxine/ pyrimethamine compared 

with monotherapy with either chloroquine or sulphadoxine/pyrimethamine in 

uncomplicated Plasmodium falciparum malaria in Laos.

Schwobel B, Jordan S, Vanisaveth V, Phetsouvanh R, Christophel EM, Phompida S,

Von Sonnenburg F, Jelinek T.

Department of Infectious Diseases and Tropical Medicine, University of Munich,

Munich, Germany Center of Malariology, Parasitology and Entomology (CMPE),

Ministry of Health, Vientiane, Lao PDR WHO Laos Office, Vientiane, Lao PDR.

In a southern border province of Lao PDR, we compared the efficacy of

antimalarial drug combinations in patients aged >/=1 year with uncomplicated

Plasmodium falciparum malaria: monotherapy with either mefloquine (MQ),

chloroquine (CQ), or sulphadoxine/pyrimethamine (SP) vs. the combination of both

CQ and SP. Follow-up time was 14 days. Of 265 P. falciparum positive patients,

119 were enrolled in the drug trial. Significantly more patients treated with CQ

than with SP developed early or late treatment failure [44.8%vs. 17.9%, relative

risk (RR) = 2.51, 95% CI 1.03-6.12]. In the SP group, 82.1% were sensitive and

17.9% were treatment failures. The combination treatment CQ plus SP resulted in

83.3% sensitivity and 16.7% treatment failures. Combination treatment has no

advantage over monotherapy with SP (RR = 1.01, 95% CI 0.8-1.3). All patients who

received MQ for treatment (total dose 25 mg/kg) were cured within the 14 days of

follow-up. The findings of this study suggest that use of CQ as first-line

treatment of uncomplicated malaria in the Lao PDR has to be reconsidered. The

combination of both CQ and SP has been discussed as a cost-effective alternative

treatment, but in our patient population achieved no better results than single

therapy with SP.

Trop Med Int Health  2003 Jan;8(1):17-18 

Malaria and amphetamine 'horse tablets' in Thailand.

Newton PN, Chierakul W, Ruangveerayuth R, Abhigantaphand D, Looareesuwan S,

White NJ.

Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Centre for

Tropical Medicine, Nuffield Department of Medicine, John Radcliffe Hospital,

Oxford, UK Mae Sot Hospital, Mae Sot, Tak Province, Thailand Division of

Narcotics, Department of Medical Sciences, Ministry of Public Health, Bangkok,

Thailand.

During recent clinical malaria research in Thailand we found a high frequency of

amphetamine misuse and withdrawal amongst patients admitted to hospital with

Plasmodium falciparum malaria. This comorbidity may cause diagnostic confusion,

alter malaria pathophysiology and lead to drug interactions.

Trop Med Int Health  2003 Jan;8(1):12-16 

Seizure disorders among relatives of Kenyan children with severe falciparum malaria.

Versteeg AC, Carter JA, Dzombo J, Neville BG, Newton CR.

Faculty of Medicine, Academic Medical Centre, University of Amsterdam,

Amsterdam, The Netherlands Neurosciences Unit, Institute of Child Health,

University of London, UK Centre for Geographic Medicine Research (Coast), Kenya

Medical Research Institute, Kilifi, Kenya.

PURPOSE: The cause of seizures in children with falciparum malaria is unclear.

In malaria endemic areas, children who develop severe falciparum malaria with

seizures may have a genetically higher risk of epilepsy or febrile seizures. We

used the history of seizures in relatives of children previously admitted with

malaria to determine if there is evidence for a familial predisposition of

seizures in children admitted with malaria and seizures or cerebral malaria.

METHODS: Family history of seizures were obtained from the parents/guardians of

81 children (35 children previously admitted with severe malaria and 46 children

matched for age who had not been admitted with severe malaria). Data were

collected on frequency, duration, age of onset, presence of fever and causes of

seizures. RESULTS: The prevalence of seizures in the relatives of children not

admitted with severe malaria was 4.3%, of whom 2.2% had a history of seizures

compatible with febrile seizures, and 1.1% with epilepsy. Overall the odds ratio

(OR) for relations of children admitted with malaria, to have a seizure disorder

was 1.41 [95% confidence interval (CI) 1.06-1.88]. There was a significant risk

of the relatives dying if they had epilepsy [relative risk 1.88 (95% CI

1.11-3.19)], but not for other seizure disorders (i.e. febrile, single or

unclassifiable seizures). CONCLUSION: Relatives of children admitted with severe

falciparum malaria are more likely to have a seizure disorder compared with

controls, but it is unclear if this is because of a genetic propensity or caused

by exogenous factors such as malaria.

Trop Med Int Health  2003 Jan;8(1):3-11 

Plasmodium falciparum multiple infections in Mozambique, its relation to other

malariological indices and to prospective risk of malaria morbidity.

Mayor A, Saute F, Aponte JJ, Almeda J, Gomez-Olive FX, Dgedge M, Alonso PL.

Centro de Investigacao em Saude da Manhica (CISM)/Ministerio de Saude, Maputo,

Mozambique Unidad de Epidemiologia y Bioestadistica, Hospital Clinic, Barcelona,

Spain Instituto Nacional de Saude, Ministerio de Saude, Maputo, Mozambique

Programa Nacional de Control de Malaria, Ministerio de Saude, Maputo,

Mozambique.

We describe the frequency of Plasmodium falciparum clones infecting individuals

living in a rural area of southern Mozambique and analyse the relationship

between multiplicity of infection, age and other malariometric indices,

including prospective risk of clinical malaria. The genotyping was based on the

use of restriction fragment length polymorphism-polymerase chain reaction

(RFLP-PCR) analysis of P. falciparum merozoite surface protein 2 (msp2). We

analysed 826 samples collected during five cross-sectional surveys from

residents of Manhica ranging in age from 4 months to 83 years. We also

determined the multiplicity of infection in samples obtained from 6-month-old

infants (n = 79) and children <10 years (n = 158) who were then treated and

followed prospectively for 1 year or 75 weeks, respectively. Multiplicity of

infection did not vary significantly during the first year of life, but

increased thereafter, and decreased during adulthood to the levels found in

infants. With increasing multiplicity of infection, there was a statistically

significant decrease in the risk of submicroscopic infections. There was also a

significant correlation between multiplicity of infection and parasite density

in infants, children <4 years of age and adults, suggesting that high densities

increase the probability of discriminating more clones in complex infections. We

found that the relationship between multiple infections and malaria morbidity is

age-dependent. In infants, the risk of subsequent episodes of clinical malaria

was related to the parasite density but not to baseline multiplicity of

infection. In older children, however, the more clones a child carried, the more

likely they were to have a clinical malaria episode, and this was true after

adjusting for parasite densities. This change in the association between

multiplicity and risk of clinical malaria may indicate a shift in the host

response to P. falciparum.

Emerg Infect Dis  2003 Jan;9(1):33-6 

A molecular surveillance system for global patterns of drug resistance in

imported malaria.

Labbe AC, Patel S, Crandall I, Kain KC.

Analysis of imported malaria in travelers may represent a novel surveillance

system for drug-resistant malaria. We analyzed consecutive falciparum malaria

isolates from Canadian travelers from 1994 to 2000, for polymorphisms in pfcrt,

dhfr, and dhps linked to chloroquine and pyrimethamine/sulfadoxine resistance.

Forty percent of isolates possessed the K76 pfcrt allele, suggesting that many

imported falciparum infections are still responsive to chloroquine. Travelers

who had recently taken chloroquine had a significantly increased risk of

harboring isolates with pfcrt resistance alleles (odds ratio = 4.47; p=0.03).

The presence of two or more mutations in dhfr or dhps was found in 64.8% (95%

confidence interval [CI] 54.6 to 73.9) and in 30.4% (95% CI 21.7 to 40.3) of

isolates, respectively, and increased significantly over the course of the

study. These molecular markers indicate that pyrimethamine/sulfadoxine

resistance is increasing and is now too high to rely on this drug as a routine

therapeutic agent to treat malaria in travelers.

Adv Parasitol  2002;52:235-64 

The consequences of reducing transmission of Plasmodium falciparum in Africa.

Snow RW, Marsh K.

Centre for Tropical Medicine, University of Oxford, John Radcliffe Hospital,

Headington, Oxford, OX3 9DU, UK.

Malaria transmission intensity in Africa varies over several log orders, from

less than one infected bite per year to more than one thousand. In this review

we examine the consequences in terms of age pattern, clinical spectrum and

overall burden of disease and discuss the possible implications for

interventions that reduce exposure to infected bites. With very low transmission

intensity, all age groups are susceptible to severe malaria. With increasing

transmission intensities, older children and adults suffer less severe disease

and with high transmission rates the majority of severe cases occur in infants

under one year of age. This pattern reflects the increasingly rapid acquisition

of immune responses that limit the life-threatening effects of malaria with

increasing exposure to the parasite. The clinical spectrum of severe malaria

varies with transmission: with high transmission, severe malarial anaemia

dominates and cerebral malaria is rare. As one moves towards lower transmission

rates, cerebral malaria accounts for an increasingly large proportion of cases.

Although the population risk of severe disease falls with age, the risk of death

at an individual level may rise with age after an initial fall from very high

case fatality rates in children aged under 6 months. Of central interest to

malaria control is how the overall amount of disease in childhood varies with

transmission. Data from a number of sources suggest that, with low transmission,

the amount of malarial disease rises with increasing exposure but that this

saturates relatively early. A key issue is whether the same pattern obtains for

deaths, both those directly due to malaria and those from all causes. The

methodological limitations of ecological comparisons between different areas are

discussed before presenting a review of attempts to use this approach in Africa.

This suggests that children living in areas of low malarial endemicity have

all-cause mortality rates about half of those of children living in areas of

moderate to high transmission. Deaths in the first year of life rise linearly

with increasing exposure to malaria over a wide range of transmission

intensities; by contrast all-cause mortality in children aged 0-4 years appears

to saturate at relatively low transmission intensities. These data suggest that

interventions that reduce exposure to malaria parasites, such as

insecticide-treated bed nets (ITNs), will have the greatest chance of a

sustained effect when used in areas where disease burdens are high but the

frequency of parasite exposure is low-to-moderate. In conditions of high

transmission, initial reductions in mortality may prove difficult to sustain as

the reduced level of transmission may still lie on the part of the curve where

mortality has saturated. However, at all levels of transmission the overall

balance of benefits, including reduced load on families and health services from

non-life-threatening malaria, favours the widespread introduction of ITNs in

endemic areas of Africa.

Am J Trop Med Hyg  2002 Dec;67(6):611-6 

Genetic diversity of Plasmodium falciparum field samples from an isolated

Colombian village.

Gomez D, Chaparro J, Rubiano C, Rojas MO, Wasserman M.

Laboratory of Biochemistry, Instituto Nacional de Salud, Bogota, Colombia.

Colombian field isolates of Plasmodium falciparum were analyzed for genetic

diversity. Fifty-three samples were collected as thick smears from patients

living in Pangui, an isolated area with low migration. While the samples were

being collected, Pangui was experiencing an epidemic outbreak of malaria. The

samples were typified using nested polymerase chain reaction (PCR) amplification

of block 2 of the merozoite surface protein 1 (MSP1) gene and nested PCR with

mutation-specific primers for position 108 of the dihydrofolate reductase enzyme

gene. The results for the circulating population of parasites in Pangui show low

diversity--four allelic forms--using MSP1 as a marker, a fact that contrasts

with data reported for certain Asian and African zones. A high percentage of

mixed infections was observed, as was high complexity of the infection. No

differential distributions were found for any allelic type.

Am J Trop Med Hyg  2002 Dec;67(6):604-10 

Impact of preseason treatment on incidence of falciparum malaria and parasite 

density at a site for testing malaria vaccines in Bandiagara, Mali.

Coulibaly D, Diallo DA, Thera MA, Dicko A, Guindo AB, Kone AK, Cissoko Y,

Coulibaly S, Djimde A, Lyke K, Doumbo OK, Plowe CV.

Malaria Research and Training Center, Faculty of Medicine, Pharmacy and

Dentistry, University of Mali, Bamako, Mali, West Africa.

Treating malaria before immunizing has been standard in malaria vaccine field

trials. To assess the impact of this practice on subsequent infection and

disease incidence, we conducted a randomized cohort study in Bandiagara, Mali.

Subjects received a treatment dose of sulfadoxine-pyrimethamine (SP) or no

treatment at the beginning of the transmission season. Cumulative and

age-specific incidence of clinical episodes was similar between the 2 groups,

but SP treatment delayed the median time to first clinical episode from 38.5 to

68 days, and after this initial period of protection, disease incidence in the

SP group quickly surpassed the incidence in the untreated group. Parasite

densities during disease episodes were lower in the SP group. SP was chosen as

the drug for initial parasite clearance for the following reasons: 1) it has

been used in previous vaccine trials; 2) our studies have found it to have >99%

efficacy in treating uncomplicated malaria in Mali compared to 85-90% efficacy

for chloroquine in this area; 3) SP is the approved second-line antimalarial

agent in Mali; and 4) its single-dose regimen ensures compliance when treatment

is directly observed.

Am J Trop Med Hyg  2002 Dec;67(6):597-603 

Low antibody responses to variant surface antigens of Plasmodium falciparum 

are associated with severe malaria and increased susceptibility to malaria attacks

in Gabonese children.

Tebo AE, Kremsner PG, Piper KP, Luty AJ.

Department of Parasitology, Institute for Tropical Medicine, University of

Tubingen, Tubingen, Germany.

We measured the levels of IgG antibodies with specificity for the variant

surface antigens (VSA) of Plasmodium falciparum in plasma samples from a cohort

of Gabonese children participating in a longitudinal case-control malaria study.

Children with mild malaria had significantly higher anti-VSA IgG responses than

their matched counterparts with severe malaria, most markedly during

convalescence and when they were healthy. Over the course of the study, almost

twice as many children who presented initially with mild rather than severe

malaria developed antibodies recognizing the VSA expressed by each of a panel of

three isolates, and those with the highest anti-VSA IgG responses had the lowest

malaria attack rates. The results suggest that the clinical outcome of P.

falciparum infection in young African children depends on their ability to both

develop and maintain a broad profile of anti-VSA IgG antibodies, and that this

ability is diminished in children who have experienced a severe malaria attack.

Am J Trop Med Hyg  2002 Dec;67(6):586-96 

Cytokine responses during acute simian Plasmodium cynomolgi and Plasmodium

knowlesi infections.

Praba-Egge AD, Montenegro S, Cogswell FB, Hopper T, James MA.

Department of Tropical Medicine and Parasitology, Tulane University School of

Public Health and Tropical Medicine, New Orleans, Louisiana 70112, USA.

Experimental infection of non-human primates with simian malaria parasites

offers a controlled system to study malarial immunity. Plasmodium cynomolgi (P.

vivax-like) and P. knowlesi (P. falciparum-like) infections in the rhesus monkey

were used as a model to test the hypothesis that initial acute infection

stimulates type 1/pro-inflammatory cytokine expression followed by a gradual

type 2/anti-inflammatory response upon re-infection. This study analyzed

cytokine gene expression (interleukin-12, interferon-gamma, tumor necrosis

factor-alpha = type 1; interleukin-4, interleukin-10 = type 2) using a

semi-quantitative reverse transcriptase-polymerase chain reaction in monkeys

infected with each of the parasites (three per group). Clinicoparasitologic and

serologic parameters were also monitored. Monkeys were re-infected to assess

whether enhanced immunity could increase parasite clearance. The immune response to 

P. cynomolgi infection in rhesus monkeys seemed to be mediated by

anti-parasite, pro-inflammatory responses during primary infection with a

transition to protective type 2 responses after repeat infection. The immune

responses to P. knowlesi infection were more varied. Anti-inflammatory responses

were more prevalent during primary infection. Repeat infection stimulated a wide

variety of responses; most included expression of tumor necrosis factor-alpha, a

cytokine that has been associated with inflammatory and host-destructive effects

(weight loss, fever, anemia). These observations further confirmed that the

simian malaria/rhesus monkey model is well suited for studies on the regulation

of immunity to acute Plasmodium infection.

Am J Trop Med Hyg  2002 Dec;67(6):578-85 

Gambian children successfully treated with chloroquine can harbor and transmit

Plasmodium falciparum gametocytes carrying resistance genes.

Sutherland CJ, Alloueche A, Curtis J, Drakeley CJ, Ord R, Duraisingh M,

Greenwood BM, Pinder M, Warhurst D, Targett GA.

Department of Infectious and Tropical Diseases, London School of Hygiene and

Tropical Medicine, London, United Kingdom. [email protected]

Polymorphisms in two genes of Plasmodium falciparum (P. falciparum multidrug

resistance 1 [pfmdr1] and P. falciparum chloroquine [CQ] resistance transporter

[pfcrt]) are associated with CQ treatment failure. We found significant linkage

disequilibrium between these loci among isolates from symptomatic Gambian

children (P = 0.026) and strong selection for the resistance-associated alleles

pfmdr1-86Tyr and pfcrt-76Thr in children with persistent or re-emerging P.

falciparum trophozoites during post-treatment follow-up (P = 1.9 x 10(-7)).

Therefore, this genotype is characteristic of resistant infections among our

study population. Since the long-term public health impact of parasites carrying

such resistant genotypes depends upon their transmissibility, we examined the

prevalence of pfmdr1-86Tyr and pfcrt-76Thr among Gambian children harboring

sexual stage parasites during post-treatment follow-up. Gametocytes that emerged

after successful treatment with CQ were significantly more likely to be of this

genotype than were those emerging after other treatments (P = 4.83 x 10(-4)),

and were infective to Anopheles mosquitoes. Therapeutic success may thus be

accompanied by public health failure as cured children pass resistance genes on

to mosquitoes at an enhanced rate.

Am J Trop Med Hyg  2002 Dec;67(6):571-7 

A biologic basis for integrated malaria control.

McKenzie FE, Baird JK, Beier JC, Lal AA, Bossert WH.

Fogarty International Center, National Institutes of Health, Bethesda, Maryland

20892, USA. 

Email: [email protected]

In a series of models of Plasmodium falciparum dynamics, spontaneous local

extinctions of the parasite sometimes occurred under steady,

perennial-transmission conditions. These extinctions occurred only with

extremely low mosquito densities or when the parameter describing the duration

of human infection-blocking immunity was at its maximum value, and,

simultaneously, those describing vector survivorship and the duration of human

infectivity were at their minimum values. The range and frequency of extinctions

increased with seasonal transmission, and decreased with the emergence of

recombinant genotypes. Here we extend the immunity parameter up to levels that

would describe a successful vaccine, and examine the combined influences of

seasonality, genotype cross-reactivity, meiotic recombination, and human

population turnover on parasite persistence. As Ross did 90 years ago, we

conclude that malaria control programs that encompass several methods and

targets of intervention are the most likely to succeed. Success is more likely

if programs are cognizant of local circumstances of transmission, and, within

that context, aim to reduce vector survivorship and human infectivity as well as

augment human immunity.

Am J Trop Med Hyg  2002 Dec;67(6):566-70 

Prevalence of Plasmodium falciparum infection in pregnant Cameroonian women.

Zhou A, Megnekou R, Leke R, Fogako J, Metenou S, Trock B, Taylor DW, Leke RF.

Department of Biology, Georgetown University, Washington, District of Columbia

20057, USA.

Between 1995 and 1998, a longitudinal study was conducted at 2 health centers in

Cameroon to determine the prevalence of Plasmodium falciparum infection in

pregnant women. There were 520 pregnant women enrolled at a rural clinic in the

village of Etoa and 199 enrolled at the Biyem Assi Clinic in the city of

Yaounde. In Etoa, pregnant women were younger, fewer took prophylaxis, and

malaria prevalence was higher compared with pregnant women in the Biyem Assi

Clinic. The prevalence of malaria infection peaked during the fourth month of

pregnancy at both sites. Age was identified as a major risk factor because women

< or = 20 years old were 1.8 and 3.4 times more likely to have malaria infection

than women > 20 years old at Etoa and the Biyem Assi Clinic after adjusting for

gravidae and other factors. The use of chemoprophylaxis and seasonality did not

have a major effect.

Am J Trop Med Hyg  2002 Dec;67(6):563-5 

Short report: Failure of the OptiMAL rapid malaria test as a tool for the

detection of asymptomatic malaria in an area of Thailand endemic for 

Plasmodium falciparum and P. vivax.

Coleman RE, Maneechai N, Ponlawat A, Kumpitak C, Rachapaew N, Miller RS,

Sattabongkot J.

Department of Entomology, Armed Forces Research Institute of Medical Sciences,

Bangkok, Thailand. 

Email: [email protected]

We evaluated the efficacy of the OptiMAL assay in a cross-sectional malaria

survey in western Thailand from April to August 2001. Expert microscopy of

Giemsa-stained thick and thin blood films was used as the gold standard.

Positive control lines were evident in 99% (1,128 of 1,137) of the assays

tested. However, 34% (384 of 1,128) of assays produced an aberrant result (a

positive P. falciparum-specific line and a negative panmalarial line).

False-positive panmalarial and Plasmodium falciparum-specific lines occurred in

25.9% (270 of 1,042) and 60.3% (628 of 1,042) of microscopy-negative samples,

respectively. Due to the preponderance of false-positive test results, it was

necessary to develop subjective criteria for test positivity based on line

intensity. For determination of assay performance during this study, we

therefore considered all test lines that were scored as intermediate or strong

as positive and lines that were faint as negative. Using these criteria, we

determined that the sensitivity of the OptiMAL assay for P. falciparum was 25%

with > 500 parasites/microl and 10.5% with > 100 parasites/microl, while for P.

vivax, the sensitivity at the same parasite rates was 100% and 41.7%,

respectively. Further studies are required to determine whether the problems we

identified are limited to this particular lot of OptiMAL assays.

Am J Trop Med Hyg  2002 Dec;67(6):555-62 

Malaria infections are randomly distributed in diverse holoendemic areas of

Papua New Guinea.

Mehlotra RK, Kasehagen LJ, Baisor M, Lorry K, Kazura JW, Bockarie MJ, Zimmerman

PA.

Center for Global Health and Diseases, Case Western Reserve University School of

Medicine, Cleveland, Ohio 44106-4983, USA.

Malaria is holoendemic in the lowlands of Papua New Guinea (PNG), and

interactions among Plasmodium species may influence prevalence of mixed

infections. Previously, field samples from a cross-sectional survey in

Dreikikir, East Sepik Province, analyzed by blood smear and polymerase chain

reaction (PCR), showed that mixed infections were common and randomly

distributed in this malaria endemic region. To evaluate further whether

Plasmodium species distribution is random, blood smear- and

PCR/sequence-specific oligonucleotide probe hybridization-based analyses of

cross-sectional survey samples were conducted in 2 additional malaria

holoendemic regions of northern PNG. Despite ecologic, species prevalence, and

transmission season differences in these new surveys, all 4 Plasmodium species

were found to be randomly distributed in each area; random distribution patterns

also were observed when study populations were divided into age groups. These

findings provide consistent evidence that Plasmodium species infections occur

independently of one another in PNG malaria holoendemic sites. This independent

occurrence suggests that age-dependent, acquired malaria immunity has limited

influence on the distribution pattern of Plasmodium species infections in

endemic human populations; infection by 1 human malaria parasite species does

not reduce susceptibility to infection by others; and malaria vaccines would

exhibit limited protection against blood-stage infection by heterologous

Plasmodium species.

Clin Invest Med  2002 Dec;25(6):262-72 

Innate immunity to malaria caused by Plasmodium falciparum.

Smith TG, Ayi K, Serghides L, Mcallister CD, Kain KC.

Department of Medicine, Clinical Science Division, University of Toronto,

Toronto, Ont.

Malaria, a widespread disease caused by protozoa of the genus Plasmodium,

contributes to the death of more than 2 million people each year. Resistance to

antimalarial drugs is increasing, and an effective vaccine has not yet been

designed. In the search for alternative means to control malaria infections,

especially those caused by the most lethal species of malaria parasite,

Plasmodium falciparum, our attention has turned to elucidating the relationships

of the parasite and human host at the molecular level. In this review, we

describe possible mechanisms by which naturally occurring genetic mutations

might confer resistance to P. falciparum and how our innate immune response

mediated by the phagocytic action of monocytes and macrophages acts as a

first-line defence in clearing malaria infections. The potential effectiveness

of novel therapies to enhance innate phagocytic clearance of malaria parasites,

particularly in nonimmune people who are at greatest risk of adverse outcomes,

is also discussed.

Med Vet Entomol  2002 Dec;16(4):461-4 

Simultaneous identification of species and molecular forms of the Anopheles

gambiae complex by PCR-RFLP.

Fanello C, Santolamazza F, della Torre A.

London School of Hygiene and Tropical Medicine, London, UK.

For differential identification of sibling species in the Anopheles gambiae

Giles complex (Diptera: Culicidae), including simultaneous separation of M and S

molecular forms within An. gambiae Giles sensu stricto, we describe a PCR-RFLP

method. This procedure is more efficient, faster and cheaper than those used

before, so is recommended for large-scale processing of field-collected larval

and adult specimens to be identified in malaria vector studies.

Med Vet Entomol  2002 Dec;16(4):452-5 

In situ hybridization to the Rdl locus on polytene chromosome 3L of Anopheles stephensi.

Andreasen MH, Ffrench-Constant RH.

Department of Infectious & Tropical Diseases, London School of Hygiene &

Tropical Medicine, London, UK. 

Email: [email protected]

We are interested in generating a Y-autosome translocation of the Resistance to

dieldrin (Rdl) locus in the malaria vector mosquito Anopheles stephensi Liston

(Diptera: Culicidae), for use in sterile insect release. To ensure stability of

the system, a recombination suppressing inversion can also be induced which

encompasses the Rdl locus. As a first step, here we report the cloning of

fragments of the Rdl gene from both An. stephensi and An. gambiae Giles using

degenerate primers in the polymerase chain reaction. These fragments encode the

second membrane-spanning region of the gamma-aminobutyric acid receptor and 

show high levels of both nucleotide and predicted amino acid identity to other

Rdl-like receptors. They confirm that, as in all other arthropod species

examined, dieldrin resistance in An. stephensi is associated with replacement of

alanine302, in this case with a serine. In situ hybridization of the Rdl probe

to polytene chromosomes of An. stephensi localizes the gene to the left arm of

chromosome 3 (3L) in region 45C. Rdl localization will enable us to identify

chromosomal rearrangements encompassing the Rdl locus and help anchor the genome sequence of An. gambiae to the polytene map.

Med Vet Entomol  2002 Dec;16(4):404-8 

Insecticide-treated plastic tarpaulins for control of malaria vectors in refugee camps.

Graham K, Mohammad N, Rehman H, Nazari A, Ahmad M, Kamal M, Skovmand O,

Guillet P, Allan R, Zaim M, Yates A, Lines J, Rowland M.

HealthNet International, Peshawar, Pakistan.

Spraying of canvas tents with residual pyrethroid insecticide is an established

method of malaria vector control in tented refugee camps. In recent years,

plastic sheeting (polythene tarpaulins) has replaced canvas as the utilitarian

shelter material for displaced populations in complex emergencies. Advances in

technology enable polythene sheeting to be impregnated with pyrethroid during

manufacture. The efficacy of such material against mosquitoes when erected as

shelters under typical refugee camp conditions is unknown. Tests were undertaken

with free-flying mosquitoes on entomological study platforms in an Afghan

refugee camp to compare the insecticidal efficacy of plastic tarpaulin sprayed

with deltamethrin on its inner surface (target dose 30 mg/m2), tarpaulin

impregnated with deltamethrin (initially > or = 30 mg/m2) during manufacture,

and a tent made from the factory impregnated tarpaulin material. Preliminary

tests done in the laboratory with Anopheles stephensi Liston (Diptera:

Culicidae) showed that 1-min exposure to factory-impregnated tarpaulins would

give 100% mortality even after outdoor weathering in a temperate climate for 12

weeks. Outdoor platform tests with the erected materials (baited with human

subjects) produced mosquito mortality rates between 86-100% for sprayed or

factory-impregnated tarpaulins and tents (average approximately 40 anophelines

and approximately 200 culicines/per platform/night), whereas control mortality

(with untreated tarpaulin) was no more than 5%. Fewer than 20% of mosquitoes

blood-fed on human subjects under either insecticide-treated or non-treated

shelters. The tarpaulin shelter was a poor barrier to host-seeking mosquitoes

and treatment with insecticide did not reduce the proportion blood-feeding. Even

so, the deployment of insecticide-impregnated tarpaulins in refugee camps, if

used by the majority of refugees, has the potential to control malaria by

killing high proportions of mosquitoes and so reducing the average life

expectancy of vectors (greatly reducing vectorial capacity), rather than by

directly protecting refugees from mosquito bites. Mass coverage with

deltamethrin-sprayed or impregnated tarpaulins or tents has strong potential for

preventing malaria in displaced populations affected by conflict.

Med Vet Entomol  2002 Dec;16(4):347-55 

Stream-bank shade and larval distribution of the Philippine malaria vector

Anopheles flavirostris.

Foley DH, Torres EP, Mueller I.

Tropical Health Program, Department of Zoology and Entomology, The University of

Queensland, Brisbane, Australia. 

Email: [email protected]

The principal malaria vector in the Philippines, Anopheles flavirostris (Ludlow)

(Diptera: Culicidae), is regarded as 'shade-loving' for its breeding sites, i.e.

larval habitats. This long-standing belief, based on circumstantial observations

rather than ecological analysis, has guided larval control methods such as

'stream-clearing' or the removal of riparian vegetation, to reduce the local

abundance of An. flavirostris. We measured the distribution and abundance of An.

flavirostris larvae in relation to canopy vegetation cover along a stream in

Quezon Province, the Philippines. Estimates of canopy openness and light

measurements were obtained by an approximation method that used simplified

assumptions about the sun, and by hemispherical photographs analysed using the

program HEMIPHOT. The location of larvae, shade and other landscape features was

incorporated into a geographical information system (GIS) analysis. Early larval

instars of An. flavirostris were found to be clustered and more often present in

shadier sites, whereas abundance was higher in sunnier sites. For later instars,

distribution was more evenly dispersed and only weakly related to shade. The

best predictor of late-instar larvae was the density of early instars.

Distribution and abundance of larvae were related over time (24 days). This

pattern indicates favoured areas for oviposition and adult emergence, and may be

predictable. Canopy measurements by the approximation method correlated better

with larval abundance than hemispherical photography, being economical and

practical for field use. Whereas shade or shade-related factors apparently have

effects on larval distribution of An. flavirostris, they do not explain it

completely. Until more is known about the bionomics of this vector and the

efficacy and environmental effects of stream-clearing, we recommend caution in

the use of this larval control method.