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EHP Library Malaria Bulletin No. 35:  April 12-25, 2002

Social Sciences and Malaria

Cent Afr J Med 2001 Jan;47(1):14-7

The knowledge and practice on malaria among community members in Zimbabwe.

Tsuyuoka R, Wagatsuma Y, Makunike B.

Japan International Co-operation Agency, P O Box 4060, Harare, Zimbabwe.

OBJECTIVES: To assess the knowledge of the cause, preventive measures and symptoms of malaria, treatment seeking behaviour on malaria and source of information about malaria among community members for the planning of effective malaria intervention. DESIGN: A cross sectional study was carried out using a questionnaire, which was administered by health workers from rural health centres. SETTING: Households in rural areas from five districts namely Uzumba Maramba Pfungwe (UMP), Hurungwe, Mount Darwin, Bulilimamangwe and Chipinge in Zimbabwe. SUBJECTS: 2,531 community members who were in charge of households sampled systematically in the area. MAIN OUTCOME MEASURES: Percentage of knowledge of transmission, signs and symptoms, prevention methods such as residual house spraying and personal protection, and treatment seeking practice on malaria. RESULTS: Knowledge of malaria transmission was generally high ranging from 57.9% to 95.9%, although there were some misconceptions such as drinking dirty water and poor hygiene. Knowledge of malaria preventive methods was varied among districts ranging from 19.4% to 93.0% about residual house spraying, and low (0.2% to 22.7%), (8.1% to 24.5%) about mosquito nets and repellents, respectively. Knowledge of malaria signs was generally high although this also varied among districts. Treatment seeking practice on malaria shows that the majority of respondents (85.4%) visit the clinic first when seeking treatment although there are other options such as shops and traditional healers. Other sources of information about malaria mentioned were, health workers (72.9%), radio (44.0%), television (37.5%), teachers (25.0%) and village community workers (10.0%). CONCLUSION: Despite widespread knowledge about the cause of malaria and symptoms, and the fairly extensive sources of health information, understanding of the preventive measures was relatively low. Appropriate health education is essential to stimulate changes in both knowledge and behaviour in malaria control activities. Schools can be effective health education tools as well as health facilities.

BMC Int Health Hum Rights 2002 Apr 15;2(1):2

Cross-sectional study of morbidity, morbidity-associated factors and cost of treatment in Ngaoundere, Cameroon, with implications for health policy in developing countries and development assistance policy.

Holtedahl K, Hurum H.

Email: [email protected]

Abstract Background. In a population-based epidemiological study in Ngaoundere, Cameroon, we studied cross-sectional child morbidity and the cost of necessary investigation and treatment. Methods. Three teams of two to three health workers visited haphazardly selected households in all major housing quarters. We asked permission to enter for a health survey. Children with cough, fever or weight loss as well as sick adults were offered free-of-charge local hospital examination and treatment. Results. From 177 households with 1777 persons 51 (2.9%) persons were referred. Thirty-five of them had undiagnosed disease threatening individual health and in many cases also public health. Seven were hospitalised, including three adults with tuberculosis. Malnutrition was diagnosed in nine small children. Four patients had AIDS, seven had malaria. Average total cost for ambulant patients was 15 USD, for hospitalised patients 110 USD. In the households, almost half of the women 16-50 years of age had no schooling. Two per cent of women and nine per cent of men were daily smokers. Coughing children were more likely than non-coughing children to live in a household with at least one smoker (OR= 3.58, 95% CI 1.72 to 7.46), and they generally lived in more poor households (P=0.018). Twelve of 16 children with weight loss were referred from households with a high poverty score. Conclusions. Adult smoking and poverty affect children's health. The cost of hospitalisation or long-lasting therapy is beyond the means of most ordinary families. Diseases with severe consequences for public health, like tuberculosis, AIDS and malaria should have national programs with free, decentralised examination and treatment. Access to generic drugs is important. A major educational effort is needed to improve public health.

Trop Med Int Health 2002 Apr;7(4):309-16

Appropriate treatment of malaria? Use of antimalarial drugs for children's fevers in district medical units, drug shops and homes in eastern Uganda.

Nshakira N, Kristensen M, Ssali F, Reynolds Whyte S.

Child Health and Development Centre, Makerere University, Kampala, Uganda, Hellerup, Denmark, Institute of Anthropology, University of Copenhagen, Copenhagen, Denmark.

OBJECTIVE To evaluate the quality of pharmaceutical care of malaria for children in eastern Uganda prescribed at government health units and drug shops, and administered by caretakers at home; and to assess its appropriateness in relation to national treatment guidelines, which recommend chloroquine over 3 days. METHODS We followed 463 children under 5 years whose caretakers attended two drug shops and two government health units to seek treatment for fever. The children were examined and the caretakers interviewed on the day of enrolment in the study (day 0), and in their homes on days 3 and 7. Data was collected on drug use prior to attending the shop or health unit, the treatment provided at these study sites, and the administration of drugs at home over the following 3 days. RESULTS Before attending the study sites, 72% of children had already been given some biomedical drugs, and 40% had received the recommended drug, chloroquine. Health workers prescribed chloroquine for 94% of the children, but only 34% of the recommended doses followed guidelines. Two-thirds of the children were prescribed an injection of chloroquine. By day 3, according to caretaker reports, about 38% of the children had received chloroquine in compliance with the instructions given by the health workers and drug shop attendants. Only 28% of the children had received chloroquine at the optimal dose of 20-30 mg/kg recommended by national policy. CONCLUSION The methods were useful for examining adherence of both caretakers and health care providers to national guidelines and the extent to which caretakers were compliant with providers' prescriptions. Chloroquine and antipyretics were the drugs of choice for fever in these areas of rural eastern Uganda. But children did not receive the recommended dosage of chloroquine because of lack of compliance on the parts of providers as well as users of health care.

Southeast Asian J Trop Med Public Health 2001 Sep;32(3):608-14

Poverty and malaria: a study in a Thai-Myanmar border area.

Panvisavas S.

Faculty of Social Sciences and Humanities, Mahidol University, Salaya, Nakhon Pathom, Thailand.

An eight-month qualitative study was conducted in 1999 in four villages of Bong Tee subdistrict, Kanchanaburi Province located along the Thai-Myanmar border area using in-depth interviews of key informants and malaria survey as research methodologies. Malaria was a serious problem in 39.6% of the families surveyed in June 1999. The four villages located in a valley covered with forests and small streams which were ideal for malaria epidemic. The structure of the villages has been changed from stable communities to disrupted ones divided along ethnic and class lines. There were 5 ethnic groups dominated by ethnic Karen. Villagers were poor and thus deprived of anti-malaria resources which allow them to remain exposed to malaria.

Southeast Asian J Trop Med Public Health 2001 Sep;32(3):588-94

Gender, mosquitos and malaria: implications for community development programs in Laputta, Myanmar.

Tin-Oo, Pe-Thet-Htoon, Khin-Thet-Wai, Parks W, Bryan J.

Tropical Health Program, Australian Center for International and Tropical Health and Nutrition, University of Queensland, Brisbane. 
Email: [email protected]

This paper examines the gender roles linked to division of labor and potential exposure to mosquitos and malaria prevention activities. A "Human Development Initiative" (HDI) Project has been launched in Laputta, a mangrove delta region of Myanmar assisted by United Nations Development Program since 1994. The project aims to improve rural community access to primary health care and provide micro-credit programs, income generation schemes, and educational opportunities as a basis for community empowerment. Women and children of low-income households are the target beneficiaries. Prior to self-care training program and distribution of self-care manuals, altogether 20 focus group discussions (separately assigned to men and women) were conducted in eight study villages between January to February 2000. The primary vector for malaria in study area is Anopheles sundaicus. Rural women were prone to malaria due to exposure to mosquitos within the peak biting period at night because of their gender assigned roles. Both men and women perceived that mosquitos commonly bite before midnight, more at dusk. Lack of awareness of correlation between mosquitos and malaria together with lack of affordability enhance either non-use or shared use of bed-nets at home. Rural women did not consider destruction of breeding places of mosquitos as their major concern. Thus, it is essential for program planners to motivate local women for more active participation in vector control measures within and beyond their households in the context of community development programs.


J Immunol 2002 May 1;168(9):4674-81

The Role of IL-18 in Blood-Stage Immunity Against Murine Malaria Plasmodium yoelii 265 and Plasmodium berghei ANKA.

Singh RP, Kashiwamura Si S, Rao P, Okamura H, Mukherjee A, Chauhan VS.

Malaria Research Group, International Center for Genetic Engineering and Biotechnology, and Institute of Pathology, Safdarjung Hospital, New Delhi, India. Department of Bacteriology, Hyogo College of Medicine, Nishinomiya, Japan.

A possible protective role of IL-18 in host defense against blood-stage murine malarial infection was studied in BALB/c mice using a nonlethal strain, Plasmodium yoelii 265, and a lethal strain, Plasmodium berghei ANKA. Infection induced an increase in mRNA expression of IL-18, IL-12p40, IFN-gamma, and TNF-alpha in the case of P. yoelii 265 and an increase of IL-18, IL-12p40, and IFN-gamma in the case of P. berghei ANKA. The timing of mRNA expression of IL-18 in both cases was consistent with a role in the induction of IFN-gamma protein expression. Histological examination of spleen and liver tissues from infected controls treated with PBS showed poor cellular inflammatory reaction, massive necrosis, a large number of infected parasitized RBCs, and severe deposition of hemozoin pigment. In contrast, IL-18-treated infected mice showed massive infiltration of inflammatory cells consisting of mononuclear cells and Kupffer cells, decreased necrosis, and decreased deposition of the pigment hemozoin. Treatment with rIL-18 increased serum IFN-gamma levels in mice infected with both parasites, delayed onset of parasitemia, conferred a protective effect, and thus increased survival rate of infected mice. Administration of neutralizing anti-IL-18 Ab exacerbated infection, impaired host resistance and shortened the mean survival of mice infected with P. berghei ANKA. Furthermore, IL-18 knockout mice were more susceptible to P. berghei ANKA than were wild-type C57BL/6 mice. These data suggest that IL-18 plays a protective role in host defense by enhancing IFN-gamma production during blood-stage infection by murine malaria.

Sci Prog 2002;85(Pt 1):89-111

Resistance to antifolates in Plasmodium falciparum, the causative agent of tropical malaria.

Warhurst DC.

PHLS Malaria Laboratory, London School of Hygiene and Tropical Medicine, London WC1F 7HT. 
Email: [email protected]

Every year there are 270 million clinical attacks of malaria and 2 million deaths, caused by the protozoan Plasmodium falciparum. Most of these cases occur in Africa. Chloroquine-resistance has led to reliance on anti-malarial antifolates, in particular the synergistic combination sulfadoxine/pyrimethamine (S/P) which targets enzymatic synthesis of folate co-factors through dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR). Resistance to S/P is now increasing and replacement antimalarials are needed. Crystal structures are not yet available for these key enzymes in the folate pathway. This review focuses on the activity of drugs on DHFR in malaria parasites, attempts to interpret differences in activity of pyrimethamine and its related drugs, and to clarify how residue changes due to point mutations determine the development of resistance. In homology-modelled P. falciparum DHFR (PfDHFR), the typical structure of four alpha-helices, 8-stranded beta-sheet, four Loops and eight Turns is clearly seen. Long polar sequences specific for Plasmodium are inserted in Turns 1 and 2. Structures immediately concerned in drug binding are beta-A, L1, alpha-B, alpha-C, T-3, beta-E, alpha-F, and beta-F. The roles of several mutations associated with resistance are discussed. In view of sequence differences in turn 3 in PfDHFR and in the human enzyme, and the marked interaction with residues of T3 of the experimental flexible antifolate WR99210 effective in pyrimethamine and cycloguanil resistance, further drug development in this area is indicated.

Indian J Med Res 2001 May;113:186-91

Investigation of malaria outbreak in Bahraich district, Uttar Pradesh.

Dhiman RC, Pillai CR, Subbarao SK.

Malaria Research Centre (ICMR), Delhi, India.

BACKGROUND & OBJECTIVES: Based on the reports of 139 fever related deaths in Jarwal primary health centre (PHC) of Bahraich district, Uttar Pradesh (UP) during April to September 1999, a study was undertaken to explore the possibility of outbreak of Plasmodium falciparum malaria in the area and reasons of outbreak. METHODS: The study was undertaken during September-October 1999 in Bahraich district, UP. The study included a parasitological and an entomological survey. Blood slides from fever cases were collected and examined following standard procedures for detection of species and stage of parasite. The resting adult mosquitoes were collected from human dwellings and cattle sheds from selected villages. Susceptibility status of Anopheles culicifacies to 4 per cent DDT and 0.05 per cent deltamethrin was determined under laboratory conditions following the WHO procedure. In vitro drug sensitivity of P. falciparum to chloroquine was also estimated. RESULTS: Overall slide positivity rate (SPR) was found to be 33.8 with a preponderance of P. falciparum (88.4%). There was an outbreak of Pf malaria in Jarwal and surrounding areas as well. Foci of P. falciparum malaria were found in Jarwal, Fakharpur and Hazoorpur PHCs around Kaisarganj PHC. In addition, P. falciparum cases, were also reported from Motipur and Tejwapur. INTERPRETATION & CONCLUSION: Poor surveillance of affected areas resulting in low annual parasite incidence (API), lack of insecticidal spray in the currently affected PHCs as the API was less than 2 and development of resistance in P. falciparum to chloroquine were found as the possible reasons for the outbreak. It is recommended that surveillance be strengthened in all PHCs of Bahraich district to contain further extension of malaria in northeastern UP.

Insect Mol Biol 2002 Apr;11(2):123-32

Isolation of cDNA clones encoding putative odourant binding proteins from the antennae of the malaria-transmitting mosquito, Anopheles gambiae.

Biessmann H, Walter MF, Dimitratos S, Woods D.

Developmental Biology Center, University of California, Irvine, CA, USA; Inscent Inc., Irvine, CA, USA.

One way of controlling disease transmission by blood-feeding mosquitoes is to reduce the frequency of insect-host interaction, thus reducing the probability of parasite transmission and re-infection. A better understanding of the olfactory processes responsible for allowing mosquitoes to identify human hosts is required in order to develop methods that will interfere with host seeking. We have therefore initiated a molecular approach to isolate and characterize the genes and their products that are involved in the olfactory recognition pathway of the mosquito Anopheles gambiae, which is the main malaria vector in sub-Saharan Africa. We report here the isolation and preliminary characterization of several cDNAs from male and female A. gambiae antennal libraries that encode putative odourant binding proteins. Their conceptual translation products show extensive sequence similarity to known insect odourant binding proteins (OBPs)/pheromone binding proteins (PBPs), especially to those of D. melanogaster. The A. gambiae OBPs described here are expressed in the antennae of both genders, and some of the A. gambiae OBP genes are well conserved in other disease-transmitting mosquito species, such as Aedes aegypti and Culex quinquefasciatus.

Curr Top Med Chem 2002 May;2(5):483-505

Perspectives in drug design against malaria.

Pattanaik P, Raman J, Balaram H.

Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, 560064, India. 
Email: [email protected]

Development of drug resistance by Plasmodium falciparum and insecticide resistance by the mosquito has lead to the resurgence of the most virulent forms of malaria. This review aims to provide a general perspective on drug design for P. falciparum malaria. Though numerous targets have been identified, new clinically useful target-specific inhibitors remain a distant prospect. This review focuses on pathways and enzymes for which some structural information and detailed biochemistry along with specificity of inhibitor action is available. Aspects of the parasite glycolytic pathway, nucleotide metabolism, proteases, redox metabolism and organelle function have been used to highlight possible targets and molecules that could inhibit their function.

Lancet 2002 Apr 13;359(9314):1311-2

Protective effects of the sickle cell gene against malaria morbidity and mortality.

Aidoo M, Terlouw DJ, Kolczak MS, McElroy PD, ter Kuile FO, Kariuki S, Nahlen BL, Lal AA, Udhayakumar V.

Division of Parasitic Diseases, National Center for Infectious Disease, Centers for Disease Control and Prevention, 30333, Atlanta, GA, USA

The high frequency of the sickle-cell haemoglobin (HbS) gene in malaria endemic regions is believed to be due to a heterozygote (HbAS) advantage against fatal malaria. Data to prospectively confirm the protection associated with HbAS against mortality are lacking. We show that HbAS provides significant protection against all-cause mortality, severe malarial anaemia, and high-density parasitaemia. This significant reduction in mortality was detected between the ages of 2 and 16 months, the highest risk period for severe malarial anaemia in this area. These data are important in understanding the role of malaria in the selection and maintenance of the sickle cell gene.

Curr Opin Infect Dis 2000 Oct;13(5):431-443

Malaria research: host-parasite interactions and new developments in chemotherapy, immunology and vaccinology.

Perlmann P, Bjorkman A.

Department of Immunology, Stockholm University, and Karolinska Institute, Infectious Diseases Unit, Karolinska Hospital, Stockholm, Sweden.

Malaria remains the major parasitic disease, with 300-500 million new infections each year. This survey covers recent advances in the field of parasite-host interactions, focusing on Plasmodium falciparum, the most virulent of the human parasites. Rapid progress in genomic research is creating a basis for the development of new drugs and vaccines. Identification of drug-resistance mutations facilitates evaluation of improved drug policies, and attempts are being made to develop new compounds that inhibit metabolic pathways that are specific to the parasite. Cytoadherence of parasitized erythrocytes to microvascular endothelium is responsible for the sequestration of parasites, causing pathology and severe disease. Newly identified molecular fine structures that mediate cytoadherence may provide new targets for specific therapies. Humoral and cell-mediated immunity induced by the parasite may be protective, but may also be harmful by generating imbalance in cytokine responses. Efforts are made to determine the pathways that give rise to protection, with vaccination being the principal goal for achieving malaria control. Different vaccine constructs are being evaluated in preclinical and clinical trials, including modified viral vectors, synthetic peptides, DNA and new adjuvants.

Science 2002 Apr 19;296(5567):545-7

Divergent regulation of dihydrofolate reductase between malaria parasite and human host.

Zhang K, Rathod PK.

Department of Chemistry, University of Washington, Seattle, WA 98195, USA, and Seattle Biomedical Research Institute, Seattle, WA 98109, USA.

For half a century, successful antifolate therapy against Plasmodium falciparum malaria has been attributed to host-parasite differences in drug binding to dihydrofolate reductase-thymidylate synthase (DHFR-TS). Selectivity may also arise through previously unappreciated differences in regulation of this drug target. The DHFR-TS of Plasmodium binds its cognate messenger RNA (mRNA) and inhibits its own translation. However, unlike translational regulation of DHFR or TS in humans, DHFR-TS mRNA binding is not coupled to enzyme active sites. Thus, antifolate treatment does not relieve translational inhibition and parasites cannot replenish dead enzyme.

Science 2002 Apr 19;296(5567):482-3

PARASITOLOGY: When the Host Is Smarter Than the Parasite.

Goldberg DE.

The wily malaria parasite has become resistant to many affordable frontline antimalarial drugs, and new drug targets are desperately needed. Reporting in a Perspective on new work (Zhang et al.), Goldberg suggests that we look for drug targets among proteins that are shared by the host and parasite but whose synthesis is regulated in a different way.

 Biochem J 2002 May 1;363(Pt 3):833-838

Glutathione synthetase from Plasmodium falciparum.

Meierjohann S, Walter RD, Muller S.

Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, MSI/WTB complex, University of Dundee, Dundee DD1 5EH, Scotland, U.K., and Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

GSH is the major low-molecular-mass thiol in most organisms. The tripeptide maintains a reduced intracellular environment and protects cellular components from damaging oxidation. GSH is synthesized by the action of two ATP-dependent enzymic steps, in which gamma-glutamylcysteine synthetase (gamma-GCS) catalyses the ligation of glutamate and cysteine and subsequently glutathione synthetase (GS) adds glycine to the dipeptide. Recently it was shown that the synthesis of gamma-glutamylcysteine is crucial for the survival of the erythrocytic stages of the malaria parasite Plasmodium falciparum by using the specific gamma-GCS inhibitor buthionine sulphoximine. In order to investigate further the synthetic pathway of the tripeptide in the parasite, GS was cloned and expressed recombinantly. The deduced amino acid sequence of P. falciparum GS shares only a moderate degree of identity with other known GSs, but the residues responsible for substrate and co-factor binding are almost all conserved, with the exception of the ones involved in gamma-glutamylcysteine binding. The protein is active as a dimer, with a subunit molecular mass of 77 kDa, and the addition of reducing reagents such as dithiothreitol is essential in maintaining enzymic activity, indicating that thiol groups are important for stability and enzymic activity. The K(app)(m) values for gamma-glutamyl-alpha-aminobutyrate, ATP and glycine were determined to be 107.1 &mgr;M, 59.1 &mgr;M and 5.04 mM, respectively, and the V(max) of 5.24+/-0.7 &mgr;mol small middle dotmin(-1) small middle dotmg(-1) was in the same range as that of the mammalian enzymes. However, the negative co-operativity observed for gamma-glutamylcysteine binding to the rat enzyme was not found for the parasite protein. This may be due to the alteration of several amino acids in the gamma-glutamylcysteine-binding site.

Med Vet Entomol 2002 Mar;16(1):67-7

Development of an exposure-free bednet trap for sampling Afrotropical malaria vectors.

Mathenge EM, Killeen GF, Oulo DO, Irungu LW, Ndegwa PN, Knols BG.

International Centre of Insect Physiology and Ecology (ICIPE), Mbita Point Research & Training Centre, Nyanza Province, Kenya.

An exposure-free bednet trap (the 'Mbita trap') for sampling of Afrotropical malaria vectors was developed during preliminary studies of mosquito behaviour around human-occupied bednets. Its mosquito sampling efficiency was compared to the CDC miniature light-trap and human landing catches under semi-field conditions in a screen-walled greenhouse using laboratory-reared Anopheles gambiae Giles sensu stricto (Diptera: Culicidae). When compared in a competitive manner (side by side), the Mbita trap caught 4.1+/-0.5 times as many mosquitoes as the CDC light-trap, hung beside an occupied bednet (P < 0.000 1) and 43.2+/-10% the number caught by human landing catches (P < 0.0001). The ratio of Mbita trap catches to those of the CDC light trap increased with decreasing mosquito density. Mosquito density did not affect the ratio of Mbita trap to human-landing catches. In a non-competitive comparison (each method independent of the other), the Mbita trap caught 89.7+/-10% the number of mosquitoes caught by human landing catches (P < 0.0001) and 1.2+/-0.1 times more mosquitoes than the CDC light trap (P = 0.0008). Differences in Mbita trap performance relative to the human landing catch under noncompetitive vs. competitive conditions were explained by the rate at which each method captured mosquitoes. Such bednet traps do not expose people to potentially infectious mosquito bites and operate passively all night without the need for skilled personnel. This trap is specifically designed to catch host-seeking mosquitoes only and may be an effective, sensitive, user-friendly and economic alternative to existing methods for mosquito surveillance in Africa.

Med Vet Entomol 2002 Mar;16(1):46-54

SCAR markers and multiplex PCR-based identification of isomorphic species in the Anopheles dirus complex in Southeast Asia.

Manguin S, Kengne P, Sonnier L, Harbach RE, Baimai V, Trung HD, Coosemans M.

Institut de Recherche pour le Developpement (IRD), Centre de Biologie et Gestion des Populations, Montpellier, France. 
Email: [email protected]

The Anopheles dirus Peyton & Harrison complex of mosquitoes (Diptera: Culicidae) comprises seven known species, including important malaria vectors in Southeast Asia. Specific identification of each species of the complex, which cannot be distinguished using morphological characters, is crucial for understanding vector ecology and implementing effective control measures. Derived from individual random amplified polymorphic DNA (RAPD) markers, sequence characterized amplified regions (SCAR) were analysed for the design of specific paired-primers. Combination of six SCAR primers resulted in the development of a simple, robust, single multiplex PCR able to identify three important malaria vectors among the four most common species (A, B, C, D) of the complex: species A from several Southeast Asian countries, species B from Perlis, Malaysia, and species C and D from Thailand.

Med Vet Entomol 2002 Mar;16(1):28-38

Malaria transmission risk variations derived from different agricultural practices in an irrigated area of northern Tanzania.

Ijumba JN, Mosha FW, Lindsay SW.

Tropical Pesticides Research Institute, Arusha, Tanzania. 
Email: [email protected]

Malaria vector Anopheles and other mosquitoes (Diptera: Culicidae) were monitored for 12 months during 1994-95 in villages of Lower Moshi irrigation area (37 degrees 20' E, 3 degrees 21' S; approximately700 m a.s.l.) south of Mount Kilimanjaro in northern Tanzania. Adult mosquito populations were sampled fortnightly by five methods: human bait collection indoors (18.00-06.00hours) and outdoors (18.00-24.00hours); from daytime resting-sites indoors and outdoors; by CDC light-traps over sleepers. Anopheles densities and rates of survival, anthropophily and malaria infection were compared between three villages representing different agro-ecosystems: irrigated sugarcane plantation; smallholder rice irrigation scheme, and savannah with subsistence crops. Respective study villages were Mvuleni (population 2200), Chekereni (population 3200) and Kisangasangeni (population approximately/= 1000), at least 7 km apart. Anopheles arabiensis Patton was found to be the principal malaria vector throughout the study area, with An. funestus Giles sensu lato of secondary importance in the sugarcane and savannah villages. Irrigated sugarcane cultivation resulted in water pooling, but this did not produce more vectors. Anopheles arabiensis densities averaged four-fold higher in the ricefield village, although their human blood-index was significantly less (48%) than in the sugarcane (68%) or savannah (66%) villages, despite similar proportions of humans and cows (ratio 1:1.1-1.4) as the main hosts at all sites. Parous rates, duration of the gonotrophic cycle and survival rates of An. arabiensis were similar in villages of all three agro-ecosystems. The potential risk of malaria, based on measurements of vectorial capacity of An. arabiensis and An.funestus combined, was four-fold higher in the ricefield village than in the sugarcane or savannah villages nearby. However, the more realistic estimate of malaria risk, based on entomological inoculation rates, indicated that exposure to infective vectors was 61-68% less for people in the ricefield village, due to the much lower sporozoite rate in An. arabiensis (ricefield 0.01%, sugarcane 0.1%, savannah 0.12%). This contrast was attributed to better socio-economic conditions of rice farmers, facilitating relatively more use of antimalarials and bednets for their families. Our findings show that, for a combination of reasons, the malaria challenge is lower for villagers associated with an irrigated rice-growing scheme (despite greater malaria vector potential), than for adjacent communities with other agro-ecosystems bringing less socio-economic benefits to health. This encourages the development of agro-irrigation schemes in African savannahs, provided that residents have ready access to antimalaria materials (i.e. effective antimalaria drugs and insecticidal bednets) that they may better afford for protection against the greater vectorial capacity of An. arabiensis from the ricefield agro-ecosystem.

Med Vet Entomol 2002 Mar;16(1):116-9

Impact of untreated bednets on prevalence of Wuchereria bancrofti transmitted by Anopheles farauti in Papua New Guinea.

Bockarie MJ, Tavul L, Kastens W, Michael E, Kazura JW.

Papua New Guinea Institute of Medical Research, Madang. 
Email: [email protected]

Despite the growing evidence that insecticide-treated mosquito nets reduce malaria morbidity and mortality in a variety of epidemiological conditions, their value against lymphatic filariasis infection and disease is yet to be established. The impact of untreated bednets on the prevalence of Wuchereria bancrofti (Cobbold) (Nematoda: Filarioidea) infection and disease was investigated on Bagabag island in Papua New Guinea, where both malaria and filariasis are transmitted by the same vector mosquitoes of the Anopheles punctulatus Donitz group (Diptera: Culicidae). Community-wide surveys were conducted recording demographic characteristics including bednet usage. Physical examinations for hydrocoele and lymphoedema were performed and blood samples assessed for filarial and malaria parasites. Mosquitoes were sampled using the all-night landing catch method and individually dissected to determine W. bancrofti infection and infective rates. Bednet usage among residents was 61% and the mean age of users (25.6 years) was similar to non-users (22.5 years). Anopheles farauti Laveran was the only species were found to contain filarial larvae: 2.7% infected (all stages), 0.5% infective (L3). The overall W. bancrofti microfilaraemia and antigenaemia rates were 28.5% and 53.1%, respectively. Bednet users had lower prevalence of W. bancrofti microfilaraemia, antigenaemia and hydrocoele rates than non-users. In comparison, untreated bednets had no effect on the prevalence and intensity of Plasmodium falciparum and P. vivax infections. The impact of bednet usage on rates of microfilaraemia and antigenaemia remained significant even when confounding factors such as age, location and sex were taken into account, suggesting that untreated bednets protect against W. bancrofti infection.

Med Vet Entomol 2002 Mar;16(1):112-5

Malaria outbreak control in an African village by community application of 'deet' mosquito repellent to ankles and feet.

Durrheim DN, Govere JM.

Communicable Disease Control, Department of Health, Nelspruit, Mpumalanga Province, South Africa. 
Email: [email protected]

The malaria vector Anopheles arabiensis Patton (Diptera: Culicidae) shows a marked predilection (> 80%) for biting the ankles and feet of human subjects, as revealed by our previous observations at Malahlapanga in the Kruger National Park, South Africa. Topical application of insect repellent, 15% deet (N,N-diethyl-3-methylbenzamide), to feet and ankles reduced the overall biting rate of An. arabiensis by 69%. A focal malaria epidemic in Albertsnek village (25 degrees 33'S, 31 degrees 59' E) near the Mozambique border, following flooding during February 2000, provided an opportunity to apply these findings of operational research for outbreak containment. Twice-nightly topical application of deet to ankles and feet of Albertsnek inhabitants was followed by rapid restoration of preepidemic malaria incidence levels after one incubation period. This encouraging outcome should be attempted in other outbreak-prone settings where infective mosquito bites are sporadic and malaria has unstable endemicity.

Med Vet Entomol 2002 Mar;16(1):109-11

Male size does not affect mating success (of Anopheles gambiae in Sao Tome).

Charlwood JD, Pinto J, Sousa CA, Ferreira C, Do RV.

Centro de Malaria e outras Doencas Tropicais, Instituto de Higiene e Medicina Tropical, Lisbon, Portugal. 
Email: [email protected]

For malaria control, the utility of transgenic vector Anopheles mosquitoes (Diptera: Culicidae) refractory to Plasmodium transmission, will depend on their interbreeding with the wild vector population. In many species, larger males are more successful in obtaining mates. In Sao Tome island, we determined that size did not affect mating success of male Anopheles gambiae Giles sensu stricto, the main malaria vector in tropical Africa. Also we showed that larval intraspecific competition is probably insignificant in this population of An. gambiae. Thus, the potential success of transgenic An. gambiae is unlikely to be affected by size selection under field conditions.

Indian J Malariol 2001 Mar-Jun;38(1-2):9-18

A randomized controlled trial comparing artemether and quinine in the treatment of cerebral malaria in Bangladesh.

Faiz MA, Rahman E, Hossain MA, Rahman MR, Yunus EB, Samad R, Hossain MA.

Department of Medicine, Chittagong Medical College, Chittagong-4000, Bangladesh.

A randomized controlled trial on 51 patients receiving artemether and 54 patients receiving quinine was undertaken to compare the effectiveness of intramuscular artemether and parenteral quinine in the treatment of cerebral malaria in adults in Bangladesh. Case fatality, fever and parasite clearance times were not significantly different in the two treatment groups. Coma resolution time was significantly delayed in artemether recipients. Results of the study suggest that treatment with artemether is as effective as parenteral quinine in the treatment of cerebral malaria in adults.

Indian J Malariol 2001 Mar-Jun;38(1-2):32-8

An outbreak of Plasmodium falciparum malaria due to Anopheles minimus in central Assam, India.

Dev V, Ansari MA, Hira CR, Barman K.

Malaria Research Centre (Field Station), Sonapur-782 402, India.

Epidemiological investigations were conducted in Nellie subcentre, PHC Jhargaon, under Morigaon district (Assam). The results of fever cases revealed 68 per cent slide positivity rate (SPR) and 40 per cent slide falciparum rate (SfR). The Pf proportion was > 87 per cent and remaining cases were P. vivax infections. An. minimus was incriminated as a malaria vector during the study period. The sporozoite rate was 3.08 per cent. The indoor man mosquito contact was 35 per bait/night as against 23 in outdoors. Results of susceptibility test revealed that the vector was still susceptible to both DDT and malathion at discriminating dosages. The study revealed that inadequate surveillance and vector control measures were contributing factors for malaria outbreak. In view of this, insecticide treated nets may be introduced to provide cost-effective control of malaria.

Indian J Malariol 2001 Mar-Jun;38(1-2):25-31

Epidemiological observations on malaria in some parts of Darrang District, Assam.

Kamal S, Das SC.

National Institute of Communicable Diseases, Rajahmundry-533 105, India.

A study on malaria conducted in tribal villages of Darrang district, Assam during April 1994 to March 1995 revealed that the malaria incidence due to Plasmodium falciparum was considerably high. Slide positivity rate (SPR) ranged between 2.3 to 45.67 per cent with transmission from May to October. P. falciparum was the dominant species (91.7 per cent) followed by P. vivax (7.25 per cent) and mixed infection (Pv + Pf = 1.05 per cent). Malaria cases were recorded throughout the year in all the age groups including infants, however, age groups between 0-1 and 21-30 years were more affected. Among 17 anophelines collected, Anopheles vagus, An. jamesii, An. crawfordi and An. minimus were the most abundant species. Known vectors of malaria like An. annularis, An. culicifacies, An. minimus, An. philippinensis and An. varuna were detected. Perennial transmission of malaria was attributed to low socio-economic conditions, poor surveillance and inadequate intervention measures.

Indian J Malariol 2001 Mar-Jun;38(1-2):19-24

A study on clinical profile of falciparum malaria in a tertiary care hospital in south India.

Harris VK, Richard VS, Mathai E, Sitaram U, Kumar KV, Cherian AM, Amelia SM, Anand G.

Department of Clinical Pathology, Christian Medical College and Hospital, Vellore-632 004, India.

Malaria continues to be a major problem in tropical countries. To study the clinical features and complications of malaria in a tertiary care hospital in south India, records of 183 patients were analysed. Among 86 patients with P. falciparum and mixed infection, 24 (28 per cent) had cerebral malaria and 32 (37 per cent) had hyperbilirubinemia. Twenty-three out of 32 (72 per cent) patients with jaundice had direct hyperbilirubinemia and elevated liver enzymes suggesting hepatocellular damage. Mortality of the order of 10 per cent was seen only in P. falciparum malaria. High incidence of hepatic involvement and hepatorenal failure were the unusual features observed in the study.

Transfusion 2002 Mar;42(3):357-62

Potential value of Plasmodium falciparum-associated antigen and antibody detection for screening of blood donors to prevent transfusion-transmitted malaria.

Silvie O, Thellier M, Rosenheim M, Datry A, Lavigne P, Danis M, Mazier D.

INSERM (National Institute for Health and Medical Research) Unit 511 (Cellular and Molecular Immunobiology of Parasitic Infections), Hospital University Center, Pitie-Salpetriere.

BACKGROUND: Malaria antibody detection is a valuable tool in the prevention of transfusion-transmitted malaria in countries with a high proportion of donors with travel exposure to malaria. The immunofluorescent antibody test (IFAT) is still the reference method, but it is not suitable for screening of blood donors. ELISA would be an interesting alternative to the IFAT, but it lacks sensitivity. STUDY DESIGN AND METHODS: To evaluate the potential value of a combined screening strategy based on malaria antigen and antibody detection, plasma samples from 203 patients infected with Plasmodium falciparum were tested with an ELISA for the detection of malaria antibodies (Malaria IgG CELISA, Cellabs) and a P. falciparum histidine-rich protein-2 kit (Malaria P.f., ICT Diagnostics) for the detection of malaria antigens. RESULTS: Among patients with positive IFAT results, CELISA had a sensitivity of 71 percent, whereas the combined screening tests (CELISA and Malaria P.f.) had a sensitivity of 88 percent (p < 0.001). Sequential samples from 50 patients were tested. The combined screening tests shortened the detection of seroconversion from 11.4 +/- 1.6 to 5.3 +/- 1.1 days (p < 0.001). CONCLUSION: Combined malaria antigen and antibody detection, with methods compatible with mass screening, may constitute an attractive alternative to the IFAT for blood donor screening.

Eur J Clin Nutr 2002 Mar;56(3):192-9

Anemia in pregnancy in rural Tanzania: associations with micronutrients status and infections.

Hinderaker SG, Olsen BE, Lie RT, Bergsjo PB, Gasheka P, Bondevik GT, Ulvik R, Kvale G.

Centre for International Health, University of Bergen, Norway, and Haydom Lutheran Hospital, Tanzania.

OBJECTIVE:: We studied the association between anemia in pregnancy and characteristics related to nutrition and infections. DESIGN:: Cross-sectional study. SETTING:: Four antenatal clinics in rural northern Tanzania. SUBJECTS/METHODS:: A total of 2547 women were screened for hemoglobin (Hb) and malaria plasmodia in capillary blood and for infections in urine. According to their Hb, they were assigned to one of five groups and selected accordingly, Hb<70 g/l (n=10), Hb=70-89 g/l (n=61), Hb=90-109 g/l (n=86), Hb=110-149 g/l (n=105) and Hb>/=150 g/l (n=50). The 312 selected subjects had venous blood drawn, were interviewed, and their arm circumference was measured. The sera were analyzed for ferritin, iron, total iron binding capacity (TIBC), cobalamin, folate, vitamin A, C-reactive protein (CRP), and lactate dehydrogenase (LD). Transferrin saturation (TFsat) was calculated. Urine was examined by dipsticks for nitrite. MAIN OUTCOME MEASURES:: Unadjusted and adjusted odds ratio (OR and AOR) of anemia with Hb<90 g/l. RESULTS:: Anemia (Hb<90 g/l) was associated with iron deficiency (low s-ferritin; AOR 3.4). The association with vitamin deficiencies were significant in unadjusted analysis (low s-folate; OR 3.1, low s-vitamin A; OR 2.6). Anemia was also associated with markers of infections (elevated s-CRP; AOR 3.5, urine nitrite positive; AOR 2.4) and hemolysis (elevated s-LD; AOR 10.1). A malaria positive blood slide was associated with anemia in unadjusted analysis (OR 2.7). An arm circumference less than 25 cm was associated with anemia (AOR 4.0). The associations with less severe anemia (Hb 90-109 g/l) were similar, but weaker. CONCLUSIONS:: Anemia in pregnancy was associated with markers of infections and nutritional deficiencies. This should be taken into account in the management of anemia at antenatal clinics. SPONSORSHIP:: The study was supported by the Norwegian Research Council (NFR) and the Centre for International Health, University of Bergen. DOI: 10.1038/sj/ejcn/1601300

Ethiop Med J 1999 Jul;37(3):173-9

Rapid diagnosis of severe malaria based on the detection of Pf-Hrp-2 antigen.

Birku Y, Welday D, Ayele D, Shepherd A.

Department of Pharmacology, Faculty of Medicine, Addis Ababa University, Addis Ababa.

Blood samples collected from 34 patients with severe malaria who were involved in antimalarial treatment studies were tested with rapid dipstick assay (Rapid Test Malaria, RTM from Quorum Diagnostics Inc., Vancouver, BC, Canada), based on the detection of Histidine Rich Protein (HRP-2) of Plasmodium falciparum. This was compared with the conventional Giemsa stained thin and thick blood smears. The study was done from March 1998 to May 1998, at the Basic Research Laboratory of the Faculty of Medicine, Addis Ababa University. Comparable number of patients (n = 32) with various diagnosis other than falciparum malaria were used as controls. The rapid dip-stick assay was positive in 31 among 34 of the severe malaria cases with sensitivity of 91.2%, specificity of 93.7%, positive predictive value (PPV) of 93.9% and negative predictive value (NPV) of 90.9%. The three cases missed by the RTM, had parasitemia of 66,000, 44,000, and 40,000/microL of blood which might be due to genetic heterogeneity of the HPR-2 expression. Among the controls, there were 2 false positive cases which may be as a result of persistent HPR-2 antigen after the clearance of peripheral parasitemia. The dip-stick method is a very quick, sensitive and specific diagnostic tool with limits of detection comparable or better than those provided by the light microscopy. The simplicity of the technique makes this method more applicable in the resource deprived laboratories of developing countries provided the kit is affordable for large scale use.

Ethiop Med J 1999 Apr;37(2):97-109

An in-vivo study of falciparum malaria sensitivity to Chloroquine in unstable malaria endemic area of central Ethiopia.

Kebede F, Taffa N, Tedla T.

PLAN International Ethiopia, P.O. Box 3062, Addis Ababa.

The role of Chloroquine as a first line drug to treat P. falciparum is almost universally becoming questionable. This study was conducted in one of the country's unstable malaria endemic area, North Shoa with the objective of assessing the in-vivo treatment efficacy of Chloroquine to falciparum malaria using the standard WHO 14 days treatment response monitoring guideline. A total of 427 patients were followed among which 87.8% showed treatment failure. This was more pronounced in children than in adults (Chi-square for trend = 8.16; P < 0.01). Clinical presentation with high grade fever on day 0 was found to be more predictive of treatment failure in children (OR = 2.06; 95% CI = 1.26, 3.36; P < 0.005). Tendency to remain febrile on subsequent follow up days was also more observed in children compared to adults. Treatment failure was further associated with high Parasite Density Index (PDI) on day 0 in all age groups (OR = 1.99; 95% CI = 1.04, 3.83; P < 0.05). Supplemented with large scale sensitivity studies, it is high time that switch to alternate drugs needs due consideration by policy makers.

J Biol Chem 2002 Apr 15; [epub ahead of print]

The structural motif in chondroitin sulfate for adhesion of plasmodium falciparum-infected erythrocytes comprises disaccharide units of 4-O-sulfated and non-sulfated N-acetylgalactosamine linked to glucuronic acid.

Chai W, Beeson JG, Lawson AM.

Glycosciences Laboratory, Imperial College School of Medicine, Harrow, Middx HA1 3UJ.

An important characteristic of malaria parasite Plasmodium falciparum-infected red blood cells (IRBCs) is their ability to adhere to host endothelial cells and accumulate in various organs. Sequestration of IRBCs in the placenta, associated with excess perinatal and maternal mortality, is mediated in part by adhesion of parasites to the glycosaminoglycan chondroitin sulfate A (CSA) present on syncytiotrophoblasts lining the placental blood spaces. To define key structural features for parasite interactions we isolated from CSA oligosaccharide fractions and established by electrospray mass spectrometry and HPLC disaccharide-composition analysis their differing chain length, sulfate content, and sulfation pattern determined. Testing these defined oligosaccharide fragments for their ability to inhibit IRBC adhesion to immobilized CSA revealed the importance of non-sulfated disaccharide units in combination with 4-O-sulfated disaccharides for interaction with IRBCs. Selective removal of 6-O-sulfates from oligo- and polysaccharides to increase the proportion of non-sulfated disaccharides enhanced activity indicating that 6-O-sulfation interferes with the interaction of CSA with IRBCs. Dodecasaccharides with four or five 4-O-sulfated and two or one non-sulfated disaccharide units, respectively, comprise the minimum chain length for effective interaction with IRBCs. Comparison of the activities of CSA and CSB oligo- and polysaccharides, with a similar sulfation pattern and content achieved from partial desulfation, demonstrated that glucuronic acid rather than iduronic acid residues are important for IRBC binding.

Trop Med Int Health 2002 Apr;7(4):304-8

Comparison of three antigen detection methods for diagnosis and therapeutic monitoring of malaria: a field study from southern Vietnam.

Huong NM, Davis TM, Hewitt S, Huong NV, Uyen TT, Nhan DH, Cong le D.

National Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam.

OBJECTIVES: To compare the sensitivity, specificity and post-treatment persistence of three commonly used rapid antigen detection methods. METHOD: We studied 252 Vietnamese patients aged from 4 to 60 years, 157 with falciparum and 95 with vivax malaria and 160 healthy volunteers. An initial blood sample was taken for microscopy, and OptiMAL, immunochromatographic test (ICT) malaria P.f./P.v. and Paracheck-Pf tests. Patients with falciparum malaria were treated with an artesunate-based combination regimen and those with vivax malaria received chloroquine. Eighty-seven patients with falciparum malaria who were initially positive for one of the antigen tests and who remained blood smear-negative underwent follow-up testing over 28 days. RESULTS: Paracheck-Pf was the most sensitive test for Plasmodium falciparum (95.8% vs. 82.6% for ICT malaria P.f./P.v. and 49.7% for OptiMAL). Specificities were all 100%. For vivax malaria, OptiMAL performed better than ICT malaria P.f./P.v. (sensitivities 73.7% and 20.0%, respectively), with 100% specificity in both cases. All tests had low sensitivities (< or = 75.0%) at parasitaemias < 1000/microl regardless of malaria species. During follow-up, Paracheck-Pf remained positive in the greatest proportion of patients, especially at higher parasitaemias (> 10,000/microl). Residual OptiMAL positivity occurred only in a relatively small proportion of patients (< 10%) with parasitaemias > 10,000/microl during the first 2 weeks after treatment. CONCLUSIONS: Although microscopy remains the gold standard for malaria diagnosis, Paracheck-Pf may prove a useful adjunctive test in uncomplicated falciparum malaria in southern Vietnam. OptiMAL had the lowest sensitivity for P. falciparum but it might have a use in the diagnosis of vivax malaria and perhaps to monitor efficacy of treatment for falciparum malaria where microscopy is unavailable.

Trop Med Int Health 2002 Apr;7(4):298-303

Malaria prevention in highland Kenya: indoor residual house-spraying vs. insecticide-treated bednets.

Guyatt HL, Corlett SK, Robinson TP, Ochola SA, Snow RW.

Wellcome Trust Research Laboratories/KEMRI, Nairobi, Kenya. 
Email: [email protected]

This study compares the effectiveness and cost-effectiveness of indoor residual house-spraying (IRS) and insecticide-treated bednets (ITNs) against infection with Plasmodium falciparum as part of malaria control in the highlands of western Kenya. Homesteads operationally targeted for IRS and ITNs during a district-based emergency response undertaken by an international relief agency were selected at random for evaluation. Five hundred and ninety homesteads were selected (200 with no vector control, 200 with IRS and 190 with ITNs). In July 2000, residents in these homesteads were randomly sampled according to three age-groups: 6 months-4 years, 5-15 years, and > 15 years for the presence of P. falciparum antigen (Pf HRP-2) using the rapid whole blood immunochromatographic test (ICT). The prevalence of P. falciparum infection amongst household members not protected by either IRS or ITN was 13%. Sleeping under a treated bednet reduced the risk of infection by 63% (58-68%) and sleeping in a room sprayed with insecticide reduced the risk by 75% (73-76%). The economic cost per infection case prevented by IRS was US$ 9 compared to US$ 29 for ITNs. This study suggests that IRS may be both more effective and cheaper than ITNs in communities subjected to low, seasonal risks of infection and as such should be considered as part of the control armamentarium for malaria prevention.

Korean J Parasitol 2002 Mar;40(1):1-7

Management of malaria in Thailand.

Silachamroon U, Krudsood S, Phophak N, Looareesuwan S.

Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.

The purpose of treatment for uncomplicated malaria is to produce a radical cure using the combination of: artesunate (4 mg/kg/day) plus mefloquine (8 mg/kg day) for 3 days: a fixed dose of artemether and lumefantrine (20/120 mg tablet) named Coartem (4 tablets twice a day for three days for adults weighing more than 35 kg): quinine 10 mg/kg 8-hourly plus tetracycline 250 mg 6-hourly for 7 days (or doxycycline 200 mg as an alternative to tetracycline once a day for 7 days) in patients aged 8 years and over: Malarone (in adult 4 tablets daily for 3 days). In treating severe malaria, early diagnosis and treatment with a potent antimalarial drug is recommended to save the patient's life. The antimalarial drugs of choice are: intravenous quinine or a parenteral form of an artemisinin derivative (artesunate i.v./i.m. for 2.4 mg/kg followed by 1.2 mg/kg injection at 12 and 24 hr and then daily for 5 dayss; artemether i.m. 3.2 mg/kg injection followed by 1.6 mg/kg at 12 and 24 hrs and then daily for 5 days; artemether i.m. (Artemotil) with the same dose of artemether or artesunate suppository (5 mg/kg) given rectally 12 hourly for 3 days. Oral artemisinin derivatives (artesunate, artemether, and dihydroartemisinin with 4 mg/kg/day) could replace parenteral forms when patients can tolerate oral medication. Oral mefloquine (25 mg/kg divided into two doses 8 hrs apart) should be given at the end of the artemisinin treatment course to reduce recrudescence.

Chembiochem 2001 Nov 5;2(11):838-43

Exploiting conformationally constrained peptidomimetics and an efficient human-compatible delivery system in synthetic vaccine design.

Moreno R, Jiang L, Moehle K, Zurbriggen R, Gluck R, Robinson JA, Pluschke G.

Swiss Tropical Institute Socinstrasse 57 4002 Basel Switzerland.

Peptide and protein mimetics are potentially of great value in synthetic vaccine design. The mimetics should function by stimulating the immune system to produce antibodies that recognize the intact parasite. Also the mimetics should be presented to the immune system in a way that leads to efficient antibody production. Here we investigate the application of cyclic peptidomimetics presented on immunopotentiating reconstituted influenza virosomes (IRIVs), a form of antigen delivery that is licensed already for human clinical use, in synthetic vaccine design. We focus on the central (NPNA)(n) repeat region of the circumsporozoite (CS) protein of the malaria parasite Plasmodium falciparum as a model system. Cyclic peptidomimetics of the NPNA repeats were incorporated into both an IRIV and (for comparison) a multiple-antigen peptide (MAP). Both IRIV and MAP delivery forms induced mimetic-specific humoral immune responses in mice, but only with the mimetic-IRIV preparations did a significant fraction of the elicited antibodies cross-react with sporozoites. The results demonstrate that IRIVs are a delivery system suitable for the efficient induction of antibody responses against conformational epitopes by use of cyclic template-bound peptidomimetics. Combined with combinatorial chemistry, this approach may have great potential for the rapid optimization of molecularly defined synthetic vaccine candidates against a wide variety of infectious agents.

Southeast Asian J Trop Med Public Health 2001 Sep;32(3):615-20

A rapid polymerase chain reaction based method for identification of the Anopheles dirus sibling species.

Huong N T, Sonthayanon P, Ketterman A J, Panyim S.

Institute of Malariology, Parasitology and Entomology, Quinhon, Vietnam.

A simple polymerase chain reaction (PCR) based method was developed to differentiate the Anopheles dirus, species A, B, C and D in Thailand using specific primers designed from species specific sequences. The PCR protocol was optimized to obtain products of 120 bp, 75 bp, 60 bp and 172 bp for species A, B, C and D, respectively. This method used a cocktail of four primer sets to identify these An. dirus sibling species. The method is very sensitive as only a small portion of mosquito was required allowing the rest of the mosquito to be used for other analyses. Specimens also kept for up to 14 years could be analyzed unambiguously from either larvae or adult. This method is advantageous over other PCR-based methods for identification of malaria vectors because it does not require any specific DNA extraction. A mosquito specimen was homogenized in 1x PCR buffer, then the supernatant directly used for PCR identification, allowing a large number of samples to be processed at the same time. It provides a simple and rapid practical method for screening An. dirus species, which is essential in malaria vector epidemiological studies in Southeast Asia.

Southeast Asian J Trop Med Public Health 2001 Sep;32(3):595-607

Malaria past and present: the case of North Sulawesi, Indonesia.

Henley D.

Royal Institute for Linguistics and Anthropology (KITLV), Leiden, The Netherlands. Email: [email protected]

The incidence and impact of malaria in North Sulawesi have declined both in the short term during the 1990s, and over a much longer timespan (though perhaps less continuously) since the end of the colonial period. The improvement already seems to have been well underway before deliberate vector control activities became extensive in the second half of the 1970s, and environmental changes affecting the Anopheles mosquito fauna, in particular the replacement of primary and secondary forest by permanent farmland, are probably the principal reasons for the long-term trend; other possible factors include the increasing use of antimalarial drugs. The well-documented decline in malaria incidence over the years 1991-1997, nevertheless, probably reflects the unprecedented scale of residual insecticide spraying in the province during that period, while the slight resurgence of the disease in the last three years corresponds to the subsequent cessation of house spraying as a result of the current economic crisis. Despite the evident importance of environmental change as a factor ameliorating the malaria situation in the long term, experience from the colonial era suggests that the prospects for deliberate environmental management (species sanitation) as an alternative malaria control strategy are poor.

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Last modified April 26, 2002