Social Sciences and Malaria

An integrated malaria control program with community participation on the Pacific Coast of Colombia.

Rojas W, Botero S, Garcia HI.

Corporacion para Investigaciones Biologicas, Medellin, Colombia.[email protected]

The study focuses on integrated malaria control in 23 communities on the Pacific Coast of Colombia, with several elements of an ecosystem approach to human health, including malaria-related sociopolitical, ecological, and economic factors. The program fostered community participation. The program presented here had 2 components: implementation and research. The first was conducted in 23 communities, 21 of which lacked adequate health services in terms of education, community participation, prompt diagnosis and complete treatment, and vector control. Research focused on specific vector control measures and the current national health services decentralization process. The project: 1) created a malaria prevention culture in the community; 2) avoided deaths from malaria (no fatal cases in the 3-year period, compared to 5-8 deaths a year previously); 3) avoided cases of cerebral malaria (no cases, as compared to 90-110 per year previously); 4) reduced malaria incidence by 45.36%; 5) decreased length of sick leave from 7.52 to 3.7 days; 6) established a permanent network of microscope technicians and 2-way radio communications; 7) integrated work by local, regional, and outside institutions; 8) demonstrated efficacy of insecticide-impregnated bednets to reduce malaria transmission.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):85-96The economic burden of malaria.

Gallup JL, Sachs JD.

Center for International Development, Harvard University, Cambridge, Massachusetts 02138, USA.[email protected]

Malaria and poverty are intimately connected. Controlling for factors such as tropical location, colonial history, and geographical isolation, countries with intensive malaria had income levels in 1995 of only 33% that of countries without malaria, whether or not the countries were in Africa. The high levels of malaria in poor countries are not mainly a consequence of poverty. Malaria is geographically specific. The ecological conditions that support the more efficient malaria mosquito vectors primarily determine the distribution and intensity of the disease. Intensive efforts to eliminate malaria in the most severely affected tropical countries have been largely ineffective. Countries that have eliminated malaria in the past half century have all been either subtropical or islands. These countries’ economic growth in the 5 years after eliminating malaria has usually been substantially higher than growth in the neighboring countries. Cross-country regressions for the 1965-1990 period confirm the relationship between malaria and economic growth. Taking into account initial poverty, economic policy, tropical location, and life expectancy, among other factors, countries with intensive malaria grew 1.3% less per person per year, and a 10% reduction in malaria was associated with 0.3% higher growth. Controlling for many other tropical diseases does not change the correlation of malaria with economic growth, and these diseases are not themselves significantly negatively correlated with economic growth. A second independent measure of malaria has a slightly higher correlation with economic growth in the 1980-1996 period. We speculate about the mechanisms that could cause malaria to have such a large impact on the economy, such as foreign investment and economic networks within the country.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):68-75Impact of Plasmodium falciparum malaria on performance and learning: review of the evidence.

Holding PA, Snow RW.

Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute, Kilifi.

Despite the growing recognition that Plasmodium falciparum malaria constitutes a major threat to child survival, the indirect consequences of disease and infection on general human development have been less well described. This review suggests that malaria in childhood is likely to have effects on general cognitive and behavioral development, which range from subtle to profound. Nevertheless, our understanding of the numbers of affected children, and the persistence of and recovery from impairment remains ill defined. Only through large long-term studies will we be able to establish the wider consequences of malaria on communities in areas of the world where malaria is endemic.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):45-56The cost-effectiveness of antenatal malaria prevention in sub-Saharan Africa.

Goodman CA, Coleman PG, Mills AJ.

Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, United Kingdom.[email protected]
Antimalarial chemoprophylaxis during pregnancy significantly increases the birth weight of babies born to primigravidae, but coverage in sub-Saharan Africa is very limited. This analysis assessed whether increasing coverage is justified on cost-effectiveness grounds. A standardized modeling framework was used to estimate ranges for the cost per discounted year of life lost averted by weekly chloroquine chemoprophylaxis and intermittent sulfadoxine-pyrimethamine (SP) treatment for primigravidae in an operational setting with moderate to high malaria transmission. The SP regimen was found to be more cost-effective than the chloroquine regimen, because of both lower costs and higher compliance. Both regimens appear to be a good value for money in comparison with other methods of malaria control and based on rough cost-effectiveness guidelines for low-income countries, even with high levels of drug resistance. However, extending the SP regimen to all gravidae and increasing the number of doses per pregnancy could make the intervention significantly less cost-effective.

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Trop Med Int Health 2001 Jun;6(6):442-8Community perceptions of a mass administration of an antimalarial drug combination in The Gambia.

De Martin S, Von Seidlein L, Deen JL, Pinder M, Walraven G, Greenwood B.

London School of Hygiene and Tropical Medicine, London, UK; Medical Research Council Laboratories, Farafenni Field Station, Fajara, The Gambia.

To test the hypothesis that widespread treatment with artemisinin derivatives can reduce malaria transmission, a mass drug administration (MDA) campaign was undertaken in an area of The Gambia in 1999. Coverage of 85% of the target population was achieved, but the intervention did not reduce overall malaria transmission. We studied the perceptions, knowledge and attitudes of the community to the MDA campaign. A validated questionnaire was administered to randomly selected MDA participants (n=90) and MDA refusers (n=71). Individuals who believed in the importance of the MDA (adjusted OR 58.3%; 95% CI 17.4-195.8) and those who were aware that a high level of participation was needed for the MDA to be successful (adjusted OR 28.1; 95% CI 10.3-75.9) were more likely to participate. Understanding that the purpose of the MDA was to reduce malaria (adjusted OR 13.9; 95% CI 5.5-35.1) and knowledge of the fact that malaria is transmitted by mosquitoes and of the clinical signs of malaria (adjusted OR 3.4; 95% CI 3.1-9.0) were associated with participation. Individuals who discussed the MDA with other villagers (adjusted OR 5.5; 95% CI 2.2-13.5) and those who attended the sensitization meeting (adjusted OR 2.6; 95% CI 1.1-6.0) were also more likely to participate. Women were significantly more likely to participate in the MDA than men (adjusted OR 3.1; 95% CI 1.5-6.2). Individuals who refused to participate were unlikely to plan participation in future MDAs. One of the most difficult challenges in the implementation of a malaria control strategy such as an MDA is to convince villagers to participate and to make them aware that a high level of participation by the community is needed for success. We found that our sensitization meetings could be improved by giving more information on how the MDA works and finding means to generate small group discussions after the meeting.

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Lancet 2001 Apr 21;357(9264):1241-7Comment in:

• Lancet. 2001 Apr 21;357(9264):1219-20
• Lancet. 2001 Apr 21;357(9264):1284-6

Effect of large-scale social marketing of insecticide-treated nets on child survival in rural Tanzania.

Schellenberg JR, Abdulla S, Nathan R, Mukasa O, Marchant TJ, Kikumbih N, Mushi AK, Mponda H, Minja H, Mshinda H, Tanner M, Lengeler C.

Ifakara Health Research and Development Centre, PO Box 53, Ifakara, Tanzania. 
[email protected]

BACKGROUND: Insecticide-treated nets have proven efficacy as a malaria-control tool in Africa. However, the transition from efficacy to effectiveness cannot be taken for granted. We assessed coverage and the effect on child survival of a large-scale social marketing programme for insecticide-treated nets in two rural districts of southern Tanzania with high perennial malaria transmission. METHODS: Socially marketed insecticide-treated nets were introduced step-wise over a 2-year period from May, 1997, in a population of 480000 people. Cross-sectional coverage surveys were done at baseline and after 1, 2, and 3 years. A demographic surveillance system (DSS) was set up in an area of 60000 people to record population, births, and deaths. Within the DSS area, the effect of insecticide-treated nets on child survival was assessed by a case-control approach. Cases were deaths in children aged between 1 month and 4 years. Four controls for each case were chosen from the DSS database. Use of insecticide-treated nets and potential confounding factors were assessed by questionnaire. Individual effectiveness estimates from the case-control study were combined with coverage to estimate community effectiveness. FINDINGS: Insecticide-treated net coverage of infants in the DSS area rose from less than 10% at baseline to more than 50% 3 years later. Insecticide-treated nets were associated with a 27% increase in survival in children aged 1 month to 4 years (95% CI 3-45). Coverage in such children was higher in areas with longer access to the programme. The modest average coverage achieved by 1999 in the two districts (18% in children younger than 5 years) suggests that insecticide-treated nets prevented 1 in 20 child deaths at that time. INTERPRETATION: Social marketing of insecticide-treated nets has great potential for effective malaria control in rural African settings.

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PubMed

Lancet 2001 Jun 9;357(9271):1837-41Control of malaria in Pakistan by applying deltamethrin insecticide to cattle: a community-randomised trial.

Rowland M, Durrani N, Kenward M, Mohammed N, Urahman H, Hewitt S.

HealthNet International, University Town, Peshawar, Pakistan

Background The standard method of malaria control in south Asia, indoor spraying of houses with residual insecticide, is becoming prohibitively expensive to implement and new approaches are needed. Since the region’s vector mosquitoes feed predominantly on domestic animals and only secondarily on human beings, to apply insecticide to surfaces of cattle instead might be more costeffective. We aimed to investigate whether domestic livestock treated with deltamethrin (applied by a sponging method) would prove toxic to mosquitoes and therefore aid in malaria control.Methods Six Afghan refugee settlements in Pakistan were randomly assigned to one of two groups. In one group livestock were treated with deltamethrin during the malaria transmission seasons of 1995 and 1997, whereas in the other group livestock were treated during the 1996 season. Malaria was monitored by passive case detection at village clinics and by cross-sectional surveillance. Mosquitoes were also monitored.Findings According to clinic records the incidence of malaria caused by Plasmodium falciparum decreased by 56% (95% CI 14-78%) and P vivax by 31% (5-50%) in livestock-treated villages. Cross-sectional surveys showed comparable decreases in parasite prevalence. The density and life expectancy of Anopheles stephensi and A culicifacies populations were reduced in treated villages. The efficacy of livestock treatment was similar to that of indoor spraying but campaign costs were 80% less. When applied in a highly endemic settlement, the incidence of falciparum malaria decreased from 280 episodes per 1000 person-years to nine episodes per 1000 person-years.Interpretations Insecticide treatment of livestock is a cost-effective and promising alternative for south Asia and other regions where primary vectors are zoophilic.

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Clin Infect Dis 2001 Aug 1;33(3):381-385Malaria Chemoprophylaxis in the Age of Drug Resistance. II. Drugs That May Be Available in the Future.

Shanks GD, Kain KC, Keystone JS.

US Army Medical Component of the Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.[email protected]

All current regimens of malaria chemoprophylaxis have serious drawbacks as a result of either suboptimal efficacy, difficulty with medication compliance, or adverse events. Two 8-aminoquinolines may be approaching registration, with primaquine having completed its prophylactic field testing and tafenoquine having begun advanced field testing at the end of 2000. Primaquine has long been used for management of relapses of malaria, but in the past decade, it has been reexamined for use in malaria prevention in order to stop infection in the liver. In field trials performed in Indonesia and Colombia, the efficacy of primaquine for malaria prevention was approximately 90%, compared with that of placebo. Because of its short half-life, primaquine requires daily administration. For adults, the prevention regimen is 30 mg base daily (0.5 mg base/kg/day), and it can probably be discontinued soon after departure from an area where malaria is endemic. To kill parasites that already exist in the liver, terminal prophylaxis is given after exposure to relapses of malaria infection; for adults, such prophylaxis usually consists of 15 mg base (0.3 mg base/kg/day) given daily for 2 weeks. Primaquine-induced gastrointestinal disturbances can be minimized if the drug is taken with food. Neither primaquine nor tafenoquine should be given to persons with glucose-6-phosphate dehydrogenase deficiency, to avoid the development of potentially severe drug-induced hemolysis. Tafenoquine is an analogue of primaquine that is more potent than the parent drug. Field trials in Kenya, Ghana, Gabon, and Southeast Asia have demonstrated an efficacy rate of approximately 90% for tafenoquine. Its long half-life allows for infrequent dosing (currently tested at 200 mg base/week), and its effect on parasites at the liver stage may allow for drug discontinuation at the time of departure from the area of endemicity.

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Gene Ther 2001 Jul;8(13):1011-23Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine.

Parker SE, Monteith D, Horton H, Hof R, Hernandez P, Vilalta A, Hartikka J, Hobart P, Bentley CE, Chang A, Hedstrom R, Rogers WO, Kumar S, Hoffman SL, Norman JA.

Vical Inc., San Diego, CA, USA.

MuStDO 5 is a multivalent plasmid DNA vaccine for malaria comprised of five plasmid DNAs encoding five proteins from Plasmodium falciparum and one plasmid DNA encoding human GM-CSF. To evaluate the safety of MuStDO 5, a series of pre-clinical studies were conducted in mice and rabbits. In pharmacology studies in mice, GM-CSF could not be detected in the serum following either intramuscular or a combined intramuscular/intradermal administration of the vaccine, but was readily detected in the muscle following intramuscular administration. In a tissue distribution study in mice, MuStDO 5 plasmid DNA was detected by PCR initially in highly vascularized tissues, while at later time-points the plasmid DNA was detected primarily at the site(s) of injection. In GLP safety studies in mice and rabbits, repeated intramuscular/intradermal administration of the MuStDO 5 vaccine was found to be safe and well tolerated without any evidence of autoimmune pathology.

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Blood 2001 Jul 15;98(2):450-457A comparison of the in vivo kinetics of Plasmodium falciparum ring-infected erythrocyte surface antigen-positive and -negative erythrocytes.

Newton PN, Chotivanich K, Chierakul W, Ruangveerayuth R, Teerapong P, Silamut K, Looareesuwan S, White NJ.

Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; the Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom; the Department of Medicine, Mae Sot Hospital, Tak Province, Thailand; and the Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.

Ring-infected erythrocyte surface antigen (RESA)-positive, Plasmodium falciparum-negative red blood cells (RBCs) are cells from which the malaria parasite has been removed by the host without the destruction of the erythrocyte (“pitting”). The survival of RESA-RBCs in vivo was assessed in 14 severe and 6 uncomplicated falciparum malaria patients. The mean RESA-RBC life of 183 hours (95% confidence interval [CI], 136-246) was longer than the median parasite clearance time of 66 hours (range, 30-108 hours) but shorter than the mean red cell life of 1027 hours (95% CI, 840-1213) (P =.0004), with a median ratio of 0.2:1.0 (range, 0.1-0.7). The estimated median percentage of parasites pitted/body transit was 0.003% (range, 0.001%-0.05%). The rate of rise of the RESA-RBC count during the first 24 hours after antimalarial treatment was significantly faster (P =.036) and the subsequent RESA-RBC survival significantly shorter (P =.017) after treatment with an artemisinin derivative than after treatment with quinine. Parasitization of red cells leads to changes in the erythrocyte that shorten their survival even if the parasite is removed subsequently. (Blood. 2001;98:450-457)

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Med Vet Entomol 2001 Jun;15(2):225-30Dipsticks for rapid detection of plasmodium in vectoring anopheles mosquitoes.

Ryan JR, Dav K, Emmerich E, Garcia L, Yi L, Coleman RE, Sattabongkot J, Dunton RF, Chan AS, Wirtz RA.

Department of Entomology, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500, USA.[email protected]

Malaria remains the most serious vector-borne disease, affecting some 300-500 million people annually, transmitted by many species of Anopheles mosquitoes (Diptera: Culicidae). Monoclonal antibodies developed against specific circumsporozoite (CS) proteins of the main malaria parasites Plasmodium falciparum and P. vivax have been used previously for enzyme-linked immunosorbent assays (ELISA), widely employed for detection of malaria sporozoites in vector Anopheles for local risk assessment, epidemiological studies and targeting vector control. However, ELISA procedures are relatively slow and impractical for field use. To circumvent this, we developed rapid wicking assays that identify the presence or absence of specific peptide epitopes of CS protein of the most important P. falciparum and two strains (variants 210 and 247) of the more widespread P. vivax. The resulting assay is a rapid, one-step procedure using a ‘dipstick’ wicking test strip. In laboratory assessment, dipsticks identified 1 ng/ mL of any of these three CS protein antigens, with sensitivity nearly equal to the CS standard ELISA. We have developed and are evaluating a combined panel assay that will be both qualitative and quantitative. This quick and easy dipstick test (VecTest Malaria) offers practical advantages for field workers needing to make rapid surveys of malaria vectors.

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Med Vet Entomol 2001 Jun;15(2):121-5Current usage of nomenclature for parasitic diseases, with special reference to those involving arthropods.

Ashford RW.

Liverpool School of Tropical Medicine, UK.[email protected]

Terminological confusion has been aggravated by efforts to develop a standardized nomenclature for parasitic diseases (SNOPAD) arising from the proposal by Kassai et al., 1988) for a standardized nomenclature of animal diseases (SNOAPAD). To restabilize international nomenclature of parasitic diseases it is recommended that, whenever appropriate, names should follow the ‘International Nomenclature of Diseases’ (IND) compiled by the Council for International Organizations for Medical Sciences (CIOMS/WHO, 1987). For diseases not included in IND, familiarity should guide the choice of name: traditional English language names of diseases should be preferred, e.g. ‘malaria’, ‘scabies’ or, for parasitic diseases having no traditional name, the taxonomic name of the causative organism should be applied, e.g. ‘Brugia timori microfilaraemia’; ‘Plasmodium malariae infection’; ‘Simulium allergy’–instead of the generic derivatives proposed by SNOPAD, i.e. brugiosis, plasmodiosis and simuliidosis, respectively. For names of new diseases or those rarely mentioned, the suffix -osis would normally take precedence. Generally, the name of choice for any disease in any language should be the vernacular term, with commonest English usage preferred for international communication, and publications should include synonyms in the list of keywords.

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BMJ 2001 Jun 30;322(7302):1567 ( Free full-text article at: http://www.bmj.com )Effect of zinc supplementation on malaria and other causes of morbidity in west African children: randomised double blind placebo controlled trial.

Muller O, Becher H, van Zweeden AB, Ye Y, Diallo DA, Konate AT, Gbangou A, Kouyate B, Garenne M.

Department of Tropical Hygiene and Public Health, Ruprecht Karls University, 69120 Heidelberg, INF 324, Germany.

Objective: To study the effects of zinc supplementation on malaria and other causes of morbidity in young children living in an area holoendemic for malaria in west Africa. Design: Randomised, double blind, placebo controlled efficacy trial. Setting: 18 villages in rural northwestern Burkina Faso. Participants: 709 children were enrolled; 685 completed the trial. Intervention: Supplementation with zinc (12.5 mg zinc sulphate) or placebo daily for six days a week for six months. Main outcome measures: The primary outcome was the incidence of symptomatic falciparum malaria. Secondary outcomes were the severity of malaria episodes, prevalence of malaria parasite, mean parasite densities, mean packed cell volume, prevalence of other morbidity, and all cause mortality. Results: The mean number of malaria episodes per child (defined as a temperature >/=37.5 degrees C with >/=5000 parasites/&mgr;l) was 1.7, 99.7% due to infection with Plasmodium falciparum. No difference was found between the zinc and placebo groups in the incidence of falciparum malaria (relative risk 0.98, 95% confidence interval 0.86 to 1.11), mean temperature, and mean parasite densities during malaria episodes, nor in malaria parasite rates, mean parasite densities, and mean packed cell volume during cross sectional surveys. Zinc supplementation was significantly associated with a reduced prevalence of diarrhoea (0.87, 0.79 to 0.95). All cause mortality was non-significantly lower in children given zinc compared with those given placebo (5 v 12, P=0.1). Conclusions: Zinc supplementation has no effect on morbidity from falciparum malaria in children in rural west Africa, but it does reduce morbidity associated with diarrhoea.

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Int J Parasitol 2001 Aug;31(10):1107-13Complete nucleotide sequence of the 6 kb element and conserved cytochrome b gene sequences among Indian isolates of Plasmodium falciparum.

Sharma I, Rawat DS, Pasha ST, Biswas S, Sharma YD.

Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, – 110029, New Delhi, India

The malaria parasite contains a nuclear genome with 14 chromosomes and two extrachromosomal DNA molecules of 6 kb and 35 kb in size. The smallest genome, known as the 6 kb element or mitochondrial DNA, has been sequenced from several Plasmodium falciparum isolates because this is a potential drug target. Here we describe the complete nucleotide sequence of this element from an Indian isolate of P. falciparum. It is 5967 bp in size and shows 99.6% homology with the 6 kb element of other isolates. The element contains three open reading frames for mitochondrial proteins-cytochrome oxidase subunit I (CoI), subunit III (CoIII) and cytochrome b (Cyb) which were found to be expressed during blood stages of the parasite. We have also sequenced the entire cyb gene from several Indian isolates of P. falciparum. The rate of mutation in this gene was very low since 12 of 14 isolates showed the identical sequence. Only one isolate showed a maximum change in five amino acids whereas the other isolate showed only one amino acid change. However, none of the Indian isolates showed any change in those amino acids of cyb which are associated with resistance to various drugs as these drugs are not yet commonly used in India.

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J Parasitol 2001 Jun;87(3):626-37Plasmodium malariae blood-stage dynamics.

McKenzie FE, Jeffery GM, Collins WE.

Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

We examine the dynamics of parasitemia, fever, and gametocytemia reflected in the preintervention charts of 180 malaria-naive U.S. neurosyphilis patients infected with the USPHS strain of Plasmodium malariae, for malariatherapy, focusing on the 84 charts for which more than 35 days of patency preceded intervention and daily records encompassed 92% or more of the duration of each infection. Inoculum size did not influence any outcome variable. Fevers (days with temperatures > or =101 F) followed patterns that fit recognized brood structures more often than did our approximations of merogony cycles (via local peaks in parasitemia), but neither closely fit textbook quartan patterns. There were no discernable patterns in gametocytemia. Successful transmission to mosquitoes increased following subcurative drug treatment but did not depend on detectable gametocytemia.

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Cad Saude Publica 2001;17 Suppl:171-9An ecosystem approach to malaria control in an urban setting.

Carrasquilla G.

Health Division, FES Foundation, Cali, Colombia.

We conducted a research project aimed at strengthening local government and the community for a sustainable malaria control strategy. The project began with a baseline diagnosis of malaria prevalence, a KAP survey, entomology, and health services delivery, after which an epidemiological study was performed to identify risk factors associated with malaria, thereafter used to plan intervention measures. A program evaluation was conducted five years later. By using an ecosystem approach to reanalyze data, this paper discusses how malaria arises from a complex interaction of cultural, economic, ecological, social, and individual factors. Intervention measures require an intersectorial and transdisciplinary approach that does not exist at the moment. Health sector leadership is limited, and there is no true community participation. Implications for research, including the use of qualitative and quantitative methods, study design, and complexity of data analysis are discussed. Finally, implications for malaria control are discussed, stressing the differences between the ecosystem and integrated disease control approaches.

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Lancet 2001 Jun 16;357(9272):1948-50Fake artesunate in southeast Asia.

Newton P, Proux S, Green M, Smithuis F, Rozendaal J, Prakongpan S, Chotivanich K, Mayxay M, Looareesuwan S, Farrar J, Nosten F, White NJ.

Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

Artesunate is a key antimalarial drug in the treatment of multidrug-resistant Plasmodium falciparum malaria in southeast Asia. We investigated the distribution of counterfeit artesunate tablets by use of the validated, simple, and inexpensive Fast Red TR dye technique. We also aimed to identify distinguishing characteristics of the fake drugs. Of 104 shop-bought “artesunate” samples from Cambodia, Laos, Myanmar (Burma), Thailand, and Vietnam, 38% did not contain artesunate. Characteristics such as cost and physical appearance of the tablets and packaging reliably predicted authenticity. The illicit trade in counterfeit antimalarials is a great threat to the lives of patients with malaria. The dye test will assist national malaria control authorities in urgently needed campaigns to stop this murderous trade.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):97-106The neglected burden of Plasmodium vivax malaria.

Mendis K, Sina BJ, Marchesini P, Carter R.

Roll Back Malaria, World Health Organization, Geneva, Switzerland. [email protected]
We estimate that the global burden of malaria due to Plasmodium vivax is approximately 70-80 million cases annually. Probably approximately 10-20% of the world’s cases of P. vivax infection occur in Africa, south of the Sahara. In eastern and southern Africa, P. vivax represents around 10% of malaria cases but < 1% of cases in western and central Africa. Outside of African, P. vivax accounts for > 50% of all malaria cases. About 80-90% of P. vivax outside of Africa occurs in the Middle East, Asia, and the Western Pacific, mainly in the most tropical regions, and 10-15% in Central and South America. Because malaria transmission rates are low in most regions where P. vivax is prevalent, the human populations affected achieve little immunity to this parasite; as a result, in these regions, P. vivax infections affect people of all ages. Although the effects of repeated attacks of P. vivax through childhood and adult life are only rarely directly lethal, they can have major deleterious effects on personal well-being, growth, and development, and on the economic performance at the individual, family, community, and national levels. Features of the transmission biology of P. vivax give this species greater resilience than the less robust Plasmodiumfalciparum in the face of conditions adverse to the transmission of the parasites. Therefore, as control measures become more effective, the residual malaria burden is likely increasingly to become that of P. vivax.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):76-84Toward a framework and indicators for monitoring Roll Back Malaria.

Remme JHE, Binka E, Nabarro D.

United Nations Development Programme/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases, World Health Organization, Geneva, Switzerland.[email protected]
Roll Back Malaria (RBM) is a new global partnership that aims to halve the malaria burden by the year 2010. A framework and indicators for monitoring the outcomes and impact of RBM have been defined through an extensive consultative process. The framework identifies critical areas for monitoring RBM action relating to 1) the impact on malaria burden, 2) improvements in malaria prevention and treatment, 3) related health sector development, and 4) support for RBM action (including partnerships). A set of RBM indicators has been defined that corresponds to these critical areas but that reflects the major variations in malaria epidemiology and the principal interventions in different parts of the world. Countries would select indicators that are appropriate for their situation. Four global indicators are proposed for use by all countries in which RBM action is under way. Data collection procedures are discussed, and it is indicated how monitoring RBM action can build on existing data-collection mechanisms.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):57-67Gaps in the childhood malaria burden in Africa: cerebral mialaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy.

Murphy SC, Breman JG.

Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, USA.

Evaluations of the African childhood malaria burden do not fully quantify the contributions of cerebral malaria (CM), CM-associated neurological sequelae, malarial anemia, respiratory distress, hypoglycemia, and pregnancy-related complications. We estimated the impact of these malaria manifestations on members of the African population < 5 years old. Calculations were based on an extensive literature review that used National Library of Medicine search engines, other bibliographic sources, and demographic data. In sub-Saharan Africa, CM annually affects 575,000 children < 5 years of age and 110,000 (approximately 19% case fatality rate [CFR]) die. Childhood survivor, of CM experience developmental and behavioral impairments: each year, 9,000-19,000 children (> 2% of survivors of CM) < 5 years of age in Africa experience neurological complications lasting > 6 months. Severe malarial anemia heavily burdens hospitals with rising admission and CFRs and with treatments that are complicated by limited and sometimes contaminated blood supplies. Severe malarial anemia occurs 1.42-5.66 million times annually and kills 190,000-974,000 (> 13% CFR) children < 5 years of age annually. Respiratory distress, hypoglycemia, and overlapping clinical manifestations cause 1.12-1.99 million cases and > 225,000 (> 18% CFR) additional deaths among African children with malaria. Maternal, placental, or fetal malaria infection during pregnancy adversely affects development and survival of fetuses and newborns through low birth weight (LBW), maternal anemia, and possibly abortion and stillbirth. Between 167,000 and 967,000 cases of malaria-associated LBW occur yearly; malaria-induced LBW kills 62,000-363,000 (> 38% CFR) newborns each year. All the gaps in the burden comprise 0.4-1.7 million deaths annually, > 50% of which are due to severe malarial anemia. These malaria-induced medical problems constitute major clinical, public health, and research challenges in that they may contribute to more than double the mortality than is generally acknowledged.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):36-44The epidemiology and burden of Plasmodium falciparum-related anemia among pregnant women in sub-Saharan Africa.

Guyatt HL, Snow RW.

Kenya Medical Research Institute/Wellcome Trust Collaborative Programme, Nairobi.[email protected]
The paucity of precise information on the burden of malaria among pregnant women has hampered effective lobbying for the inclusion of preventative strategies against malaria in Safe Motherhood Initiatives. This article reviews the evidence on the coincidental risks of malaria and anemia in Africa and attempts to estimate the probable burden of malaria-related severe anemia in this susceptible group. Twenty-six studies on hemoglobin levels in all-parity pregnant women throughout this region could be matched with a malaria parasite ratio in children < 15 yr old (a measure of the intensity of transmission). In areas with no malaria, the mean hemoglobin levels were markedly higher than those found in areas with stable malaria transmission, though changes with increasing intensity of transmission were unclear. Eighteen studies from areas with stable malaria transmission in sub-Saharan Africa suggested that the median prevalence of severe anemia in all-parity pregnant women is approximately 8.2%. Assuming that 26% of these cases are due to malaria, it is suggested that as many as 400,000 pregnant women may have developed severe anemia as a result of infection with malaria in sub-Saharan Africa in 1995.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):28-35The burden of malaria in pregnancy in malaria-endemic areas.

Steketee RW, Nahlen BL, Parise ME, Menendez C.

Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, Atlanta, Georgia 30333, USA.[email protected]
Pregnant women in malarious areas may experience a variety of adverse consequences from malaria infection including maternal anemia, placental accumulation of parasites, low birth weight (LBW) from prematurity and intrauterine growth retardation (IUGR), fetal parasite exposure and congenital infection, and infant mortality (IM) linked to preterm-LBW and IUGR-LBW. We reviewed studies between 1985 and 2000 and summarized the malaria population attributable risk (PAR) that accounts for both the prevalence of the risk factors in the population and the magnitude of the associated risk for anemia, LBW, and IM. Consequences from anemia and human immunodeficiency virus infection in these studies were also considered. Population attributable risks were substantial: malaria was associated with anemia (PAR range = 3-15%), LBW (8-14%), preterm-LBW (8-36%), IUGR-LBW (13-70%), and IM (3-8%). Human immunodeficiency virus was associated with anemia (PAR range = 12-14%), LBW (11-38%), and direct transmission in 20-40% of newborns, with direct mortality consequences. Maternal anemia was associated with LBW (PAR range = 7-18%), and fetal anemia was associated with increased IM (PAR not available). We estimate that each year 75,000 to 200,000 infant deaths are associated with malaria infection in pregnancy. The failure to apply known effective antimalarial interventions through antenatal programs continues to contribute substantially to infant deaths globally.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):18-27All-cause mortality among young children in western Kenya. VI: the Asembo Bay Cohort Project.

McElroy PD, ter Kuile FO, Hightower AW, Hawley WA, Phillips-Howard PA, Oloo AJ, Lal AA, Nahlen BL.

Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.[email protected]
Although all-cause mortality has been used as an indicator of the health status of childhood populations, such data are sparse for most rural areas of sub-Saharan Africa, particularly community-based estimates of infant mortality rates. The longitudinal follow-up of more than 1,500 children enrolled at birth into the Asembo Bay Cohort Project (ABCP) in western Kenya between 1992 and 1996 has provided a fixed birth cohort for estimating all-cause mortality over the first 5 yr of life. We surveyed mothers and guardians of cohort children in early 1999 to determine survival status. A total of 1,260 households were surveyed to determine the survival status of 1,556 live births (99.2% of original cohort, n = 1,570). Most mothers (66%) still resided but 27.5% had migrated, and 5.5% had died. In early 1999, the overall cumulative incidence of all-cause mortality for the entire 1992-1996 birth cohort was 26.5% (95% confidence interval, 24.1-28.9%). Neonatal and infant mortality were 32 and 176 per 1,000 live births, respectively. These community-based estimates of mortality in the ABCP area are substantially higher than for Kenya overall (nationally, infant mortality is 75 per 1,000 live births). The results provide a baseline description of all-cause mortality among children in an area with intense Plasmodium falciparum transmission and will be useful in future efforts to monitor changes in death rates attributable to control programs for specific diseases (e.g., malaria and HIV/AIDS) in Africa.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):12-7The public health impact of chloroquine resistance in Africa.

Trape JF.

Laboratoire de Paludologie, Institut de Recherche pour le Developpement (IRD, formerly ORSTOM), Dakar, Senegal.[email protected]
Between 1978 and 1988 Plasmodium falciparum resistance to chloroquine has been reported in all countries of tropical Africa. Despite the intensification of resistance during the last 2 decades, chloroquine remains in 2000 the first-line treatment for malaria in most of these countries. Here we review published data on the public health impact of antimalarial drug resistance in Africa. These data show that since the late 1980s convincing evidence of a major public health impact of the spread of chloroquine resistance has been available. Hospital studies in various African countries have documented a 2- or 3-fold increase in malaria deaths and admissions for severe malaria, an increase temporally related to the emergence of chloroquine resistance. Data from sentinel demographic surveillance systems in Senegal indicated that mortality attributable to malaria in children increased by as much as 6-fold among populations where low levels of malaria mortality had been achieved because of efficient health services before the emergence of chloroquine resistance. Increasing incidence of severe malarial anemia also contributed to human immunodeficiency virus dissemination. The dramatic impact of chloroquine resistance on malaria mortality has long been underestimated because only a low proportion of malaria attacks are potentially lethal among persons continuously exposed since birth to high levels of transmission. There is an urgent need to change treatment policies in Africa.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2 Suppl):1-11The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden.

Breman JG.

Fogarty International Center, National institutes of Health, Bethesda, Maryland 20892-2220, USA.[email protected]
Malarious patients experience asymptomatic parasitemia; acute febrile illness (with cerebral damage, anemia, respiratory distress, hypoglycemia); chronic debilitation (anemia, malnutrition, nervous system-related sequelae); and complications of pregnancy (anemia, low birth weight, increased infant mortality). These manifestations in patients, communities, and countries reflect intrinsic (human, parasite, mosquito) and extrinsic (environmental, social, behavioral, political, and economic conditions as well as disease-control efforts) determinants. At a minimum, between 700,000 and 2.7 million persons die yearly from malaria, over 75% of them African children. Between 400 and 900 million acute febrile episodes occur yearly in African children under 5 yr of age living in endemic areas. Although about half of these children are parasitemic, all merit consideration of malaria-specific therapy, which is becoming more problematic because of parasite resistance to drugs. These numbers will more than double over the next 20 yr without effective control. Fewer than 20% of these febrile episodes and deaths come to the attention of any formal health system. The relatively few ill patients who have any contact with the health services represent the “ears of the hippopotamus.” Greatly intensified research activities and control of the intolerable burden of malaria are mandatory if economic development is to accelerate in Africa. In particular, support should be targeted to understanding and preventing malaria-induced anemia, hypoglycemia, effects on pregnancy, and neurologic and developmental impairment. To decrease and stop transmission of this intolerable scourge, there is an urgent need for malaria vaccines, newer drugs, and better vector control methods as well as the ability to improve current technologies and use them more efficiently.

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  Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):9-11Limited polymorphism in Plasmodium falciparum sexual-stage antigens.

Niederwieser I, Felger I, Beck HP.

Swiss Tropical Institute, Basel.

In areas highly endemic for malaria, individuals are frequently found to be infected simultaneously with multiple Plasmodium falciparum clones. This raises the question of whether all parasite clones produce gametocytes equally or whether gametocytogenesis is suppressed in some clones. In order to assess this in epidemiological studies, polymorphic genes specifically expressed in gametocytes could be analyzed by both amplification of genomic DNA from blood samples and by reverse transcribed polymerase chain reaction amplifying expressed gametocyte-specific genes only. Here we report the analysis of diversity in the three gametocyte-specific genes Pfs16, Pfs48/45, and Pfs230. In addition to the previously published data, limited polymorphism was found in the coding sequences of Pfs16 and Pfs48/45. Larger polymorphism was identified in Pfs230, which might allow the development of a discriminating PCR-based genotyping scheme for transmission studies. However, the limited polymorphism in Pfs16 and Pfs48/45 renders these molecules poorly useful for such studies.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):6-8Short report: increased susceptibility to Plasmodium malariae in pregnant alpha(+)-thalassemic women.

Mockenhaupt FP, Rong B, Till H, Thompson WN, Bienzle U.

Institute of Tropical Medicine Berlin, Medical Faculty Charite, Humboldt-University Berlin, Germany.

The influence of alpha(+)-thalassemia on malaria in pregnancy was assessed in a cross-sectional study of 530 women in Ghana. Plasmodial infections, alpha(+)-thalassemia, serum levels of C-reactive protein, and antimalarial drugs in urine were determined. The alpha-globin genotypes did not correlate with the prevalence of Plasmodium falciparum-infection and parasite densities. However, Plasmodium malariae tended to be more frequent in alpha(+)-thalassemic women (P = 0.05). Excluding women with residual antimalarials, a significant excess of P. malariae was observed in alpha(+)-thalassemic individuals. Febrile responses (P = 0.05) and inflammation (CRP > 0.6 mg/dl, P = 0.06) appeared to be less common in infected alpha(+)-thalassemic women and were also comparatively rare in parasitemic individuals who harbored double species infections with P. falciparum and P. malariae. Plasmodium malariae may influence the pathogenesis of falciparum malaria leading to a low prevalence of inflammation and febrile responses in alpha(+)-thalassemic women.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):58-66Hemoglobin concentration in children in a malaria holoendemic area is determined by cumulated Plasmodium falciparum parasite densities.

Ekvall H, Premji Z, Bennett S, Bjorkman A.

Unit of Infectious Diseases, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden. [email protected]
In malaria holoendemic areas children are anemic, but the exact influence of falciparum malaria on hemoglobin (Hb) concentration remains largely unsettled. Prospective data were therefore collected in children < 24 months of age during five months in a Tanzanian village. Children with mean asymptomatic parasitemia > or = 400/microl had lower median Hb levels during the study than those with mean density < 400/microl. The difference was 9.7 g/L (95% confidence interval [CI] 2.8-17). In children with one or more clinical malaria episodes, the median Hb was 8.3 g/L (95% CI 0.9-16) lower than those without episode. If early treatment failure was recorded, the immediate effect on Hb was particularly important with a mean drop of 17 g/L. Interestingly, at study-end the Hb concentration represented a function of the area under the parasitemia curve (AUPC) during the previous five months, adjusting for age. In conclusion, stepwise deterioration in median Hb levels was found by asymptomatic parasitemia, clinical malaria episode, and most significantly, treatment failure.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):32-4Comparison of direct and membrane feeding methods to infect Anopheles arabiensis with Plasmodium falciparum.

Awono-Ambene HP, Diawara L, Robert V.

Laboratoire de Paludologie, Institut de Recherche pour le Developpement, Dakar, Senegal.

Two standard methods are available to infect mosquitoes with malaria parasites: direct feeding through the skin of the gametocyte carrier, and membrane feeding. Anopheles arabiensis collected at larval stages and reared in an insectary were fed in parallel by feeding on Plasmodium falciparum gametocyte carriers and by membrane feeding on venous blood of the same gametocyte carriers. Infection of mosquitoes was assessed at Day 7 post bloodmeal by oocyst count of the mosquito midguts. The following parameters were not significantly different between the two methods: the percentage of gametocyte carriers infective for at least one mosquito (52.4% through the skin versus 57.1% through the membrane), the mean infection rate of mosquitoes (10.0% versus 11.3%), the geometric mean oocyst number per mosquito (2.51 versus 3.83). In conclusion, infection of mosquitoes by membrane feeding was similar to infection by direct feeding. Most of the volunteers preferred venipuncture to mosquito bites.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):28-31Short report: differences in dihydrofolate reductase but not dihydropteroate synthase alleles in Plasmodium falciparum isolates from geographically distinct areas in Malaysia.

Cox-Singh J, Zakaria R, Abdullah MS, Rahman HA, Nagappan S, Singh B.

Faculty of Medicine and Health Sciences, University Malaysia Sarawak.

Dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) alleles were typed in 67 Malaysian Plasmodium falciparum isolates. The isolates were collected from two geographically distinct locations: 51 from Sabah, Malaysian Borneo, where sulfadoxine/pyrimethamine (SDX/PYR) is used to treat uncomplicated malaria and 16 from Peninsular Malaysia where in vivo resistance to SDX/PYR has been reported. A total of seven dhps alleles were identified with no significant difference in allele frequency between the 2 populations. Two of the dhps alleles described here have not been previously reported. Four dhfr alleles were detected in 67 P. falciparum isolates. Eighty-seven percent of the isolates from the Peninsula, where clinical SDX/PYR failure has been reported, had dhfr alleles with triple point mutations while all of the isolates from Sabah had dhfr alleles with 2 or less point mutations. The difference in dhfr allele frequency between the two populations was highly significant. There was no correlation between in vitro PYR response and accumulation of dhfr point mutations.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):20-3Diagnosis of imported malaria by Plasmodium lactate dehydrogenase (pLDH) and histidine-rich protein 2 (PfHRP-2)-based immunocapture assays.

Iqbal J, Hira PR, Sher A, Al-Enezi AA.

Department of Microbiology, Faculty of Medicine, Kuwait University, Safat. [email protected]
This study was conducted to evaluate the performance of two rapid non-microscopic assays: Plasmodium lactate dehydrogenase (pLDH) assay (OptiMAL) and Plasmodium falciparum histidine-rich protein 2 (PfHRP-2) assay (ICT Malaria). The assays were used to detect malaria infection in 515 immigrants living in Kuwait. The performance of both assays was compared to that of microscopy of Giemsa-stained thick blood films and to each other. Of the 515 patients tested, 163 were positive for malaria parasites by microscopy of thick blood film. Of these, 87 were infected with Plasmodium vivax parasites, 63 with P. falciparum, 1 with Plasmodium malariae, and 12 had mixed infections of P. falciparum and P. vivax. The PfHRP-2 assay detected 53 P. falciparum infections and, as expected, failed to detect all but one case of P. vivax. Three cases of mixed infections were also not detected by this assay. The pLDH assay detected 56 P. falciparum cases and 77 P. vivax infections but failed to detect 4 cases of mixed infections. Compared to microscopy, the performance of both the assays to diagnose P. falciparum infection was comparable. The sensitivity for the PfHRP-2 assay was 82% with a specificity of 99.0% and for the pLDH assay the sensitivity was 89% with a specificity of 99.5%. The PfHRP-2 assay detected 4 false positive cases, 2 of which were also detected by the pLDH assay. These patients reported treatment with chloroquine in the last 2-5 weeks. Though the immunocapture diagnostic assays may be helpful in certain situations, microscopy of thick blood film is still the method of choice in diagnosing imported malaria.

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Am J Trop Med Hyg 2001 Jan-Feb;64(1-2):1-5CR1 density polymorphism on erythrocytes of falciparum malaria patients in Thailand.

Nagayasu E, Ito M, Akaki M, Nakano Y, Kimura M, Looareesuwan S, Aikawa M.

The Institute of Science and Technology, Tokai University, Isehara, Japan.

Complement receptor type 1 (CR1) on erythrocytes shows an inherited numerical polymorphism which correlates with a HindIII-RFLP (restriction fragment length polymorphism) of the CR1 gene in various populations. To investigate the relationship between CR1 density polymorphism and disease severity, we typed 185 Thai patients with acute falciparum malaria (55 severe and 130 uncomplicated) for their genotypes of this polymorphism. The level of expression of erythrocyte CR1 from 42 randomly selected patients was measured by enzyme-linked immunosorbent assay (ELISA). We observed a significantly higher frequency of homozygotes of the CR1 low density allele (LL) among the severe group as compared to the uncomplicated group (P = 0.005). CR1 expression on erythrocytes from patients with the LL genotype was significantly lower than homozygotes with the high density allele (HH) (P < 0.0001) and heterozygotes (HL) (P = 0.013). The results suggest that a genetically-determined low CR1 density on erythrocytes may be a risk factor for developing a more severe form of malaria in Thai subjects.

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Trends Parasitol 2001 Jul;17(7):331-7Parasite adhesion and immune evasion in placental malaria.

Beeson JG, Reeder JC, Rogerson SJ, Brown GV.

Dept of Medicine, University of Melbourne, Royal Melbourne Hospital, VIC 3050, Parkville, Australia

Parasite sequestration in the placenta is a key feature of infection by Plasmodium falciparum during pregnancy and is associated with severe adverse outcomes for both mother and baby. Here, James Beeson and colleagues draw together the findings of recent studies on parasite mechanisms that mediate this process. They review evidence for novel parasite variants that appear able to evade pre-existing immunity, for the adhesion of P. falciparum-infected erythrocytes to placental glycosaminoglycans (and the molecular basis of these parasite properties) and for the expression of var genes encoding the variant antigen and adhesive ligand P. falciparum-erythrocyte membrane protein 1 (PfEMP1).

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Trends Parasitol 2001 Jul;17(7):307-9Rapid diagnostic techniques for malaria control.

Wongsrichanalai C.

Armed Forces Research Institute of Medical Sciences (AFRIMS), 315/6 Rajvithi Road, 10400, Bangkok, Thailand

The past decade was a milestone in the development of malaria diagnostic technology. Today, a variety of simplified and rapid malaria diagnostic devices, collectively referred to as ‘dipsticks’, is available. This paper discusses the potential roles of these devices, and obstacles to their use, in supporting malaria control strategies.

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Trop Med Int Health 2001 Jun;6(6):458-62PCR-based ELISA technique for malaria diagnosis of specimens from Thailand.

Laoboonchai A, Kawamoto F, Thanoosingha N, Kojima S, Scott Miller RR, Kain KC, Wongsrichanalai C.

Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.

We performed a field evaluation of polymerase chain reaction (PCR)-based enzyme-linked immuno-sorbent assays (ELISA) for the diagnosis of malaria. A commercially available PCR-ELISA microplate hybridization (MPH) assay was used. Blood specimens were collected from 300 volunteers seeking care at malaria clinics in Thailand. Examination of 200 high power fields by Giemsa-stained thick and thin smear (GTTS) revealed 51 P. falciparum (Pf), 45 P. vivax (Pv), seven mixed Pf-Pv infections. These plus a random sample of 48 GTTS-negative specimens were selected for this study. All 151 specimens were processed for parasite DNA extraction and assayed by PCR-MPH. The target DNA sequence of the 18S small subunit ribosomal RNA (SSUrRNA) gene was amplified by PCR and hybridized with species-specific probes for Pf, Pv, P. malariae (Pm) and P. ovale (Po) immobilized in the wells of the microtiter plate and detected by colorimetric assay. Colour development was assessed at an optical density (OD) of 405 nm. An absorbance reading of > or = 0.1 was used as a positive cut-off. In comparison with GTTS results, PCR-MPH sensitivity was 91.4% (53/58, 95% CI 84.2-98.6) for Pf, 94.2% (49/52, 87.9-100) for Pv and specificity was 95.8% (46/48, 95% CI 90.2-100). There was statistically significant positive correlation between parasite densities < or = 7000/microl blood and absorbance reading, suggestive of PCR-MPH being semiquantitative. PCR-MPH also detected additional Pf and Pv cases as well as Pm and Po.

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Trop Med Int Health 2001 Jun;6(6):429-34Therapeutic efficacy of sulphadoxine/pyrimethamine and susceptibility in vitro of P. falciparum isolates to sulphadoxine-pyremethamine and other antimalarial drugs in Malawian children.

Takechi M, Matsuo M, Ziba C, MacHeso A, Butao D, Zungu IL, Chakanika I, Bustos MD.

Community Health Sciences Unit, Ministry of Health and Population, Malawi; Research Institute of Tropical Medicine, Ministry of Health, Philippines.

Since 1993 sulphadoxine/pyrimethamine (SP) has been used as the first-line drug for uncomplicated Plasmodium falciparum malaria in Malawi. To investigate the current efficacy of SP and other antimalarial drug resistance, we studied in vivo and in vitro responses to SP, chloroquine (CQ), mefloquine (MF), quinine (QN), and halofantrine (HF) in Salima, central Malawi. In a follow-up of 14 days, nine (13.8%) of 65 children under five showed RII/RIII parasitological resistance, and in in vitro microtests 18 (62.1%) of 29 isolates showed <90% inhibition of schizont maturation at pyrimethamine 75 nmol/l blood medium mixture, indicating resistance. The discrepancy between in vivo and in vitro results might be partially explained by acquired immunity in this holoendemic area. In vitro one (3.4%) of 29 isolates failed schizont inhibition at 1.6 &mgr;mol/l blood of CQ, indicating resistance. Compared with an in vitro study conducted in 1988 in another region of Malawi using the same cut-off point, the proportion of resistant isolates had decreased significantly (P < 0.01). Although 31% of isolates were borderline, showing schizont maturation at 0.8 &mgr;mol/l blood but no schizonts at 1.6 &mgr;mol/l in our study, the results suggest possible recovery of CQ sensitivity after long-term absence of drug pressure. Resistance remains a major problem in malaria control. Monitoring resistance patterns in vitro provides early warning signs of impending loss of therapeutic efficacy of the standard treatment, and may detect changing patterns in alternative drug resistance.

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Trop Med Int Health 2001 Jun;6(6):423-8Diagnostic accuracy and case management of clinical malaria in the primary health services of a rural area in south-eastern Tanzania.

Font F, Alonso Gonzalez M, Nathan R, Kimario J, Lwilla F, Ascaso C, Tanner M, Menendez C, Alonso PL.

Unidad de Epidemiologia y Bioestadistica, Hospital Clinic/IDIBAPS, Universidad Barcelona, Spain; Ifakara Health Research and Development Center, Ifakara, Tanzania; Swiss Tropical Institute, Basle, Switzerland.

Malaria control continues to rely on the diagnosis and prompt treatment of both suspected and confirmed cases through the health care structures. In south-eastern Tanzania malaria is one of the leading causes of morbidity and mortality. The absence of microscopic examination in most of the health facilities implies that health workers must rely on clinical suspicion to identify the need of treatment for malaria. Of 1558 randomly selected paediatric consultations at peripheral health facilities throughout Kilombero District, 41.1% were diagnosed by the attending health worker as clinical malaria cases and 42.5% prescribed an antimalarial. According to our malaria case definition of fever or history of fever with asexual falciparum parasitaemia of any density, 25.5% of all children attending the health services had malaria. This yielded a sensitivity of 70.4% (IC95%=65.9-74.8%) and a specificity of 68.9% (IC95%=66.2-71.5%). Accordingly, 30.4% of confirmed cases left with no antimalarial treatment. Among malaria-diagnosed patients, 10% were underdosed and 10.5% were overdosed. In this area, as in many African rural areas, the low diagnostic accuracy may imply that the burden of malaria cases may be overestimated. Greater emphasis on the functioning and quality of basic health services in rural endemic areas is required if improved case management of malaria is to help roll back this scourge.

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Mol Biol Evol 2001 Jul;18(7):1353-64Evidence for Recent Population Expansion in the Evolutionary History of the Malaria Vectors Anopheles arabiensis and Anopheles gambiae.

Donnelly MJ, Licht MC, Lehmann T.

Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia. Division of Parasite and Vector Biology, Liverpool School of Tropical Medicine, Liverpool, England.

Gene flow in malaria vectors is usually estimated based on differentiation indices (e.g., F(ST)) in order to predict the contemporary spread of genes such as those conferring resistance to insecticides. This approach is reliant on a number of assumptions, the most crucial, and the one most likely to be violated in these species, being mutation-migration-drift equilibrium. Tests of this assumption for the African malaria vectors Anopheles gambiae and Anopheles arabiensis are the focus of this study. We analyzed variation at 18 microsatellite loci and the ND5 region of the mitochondrial genome in two populations of each species. Equilibrium was rejected by six of eight tests for the A. gambiae population from western Kenya and by three tests in eastern Kenya. In western Kenya, all departures from equilibrium were consistent with a recent population expansion, but in eastern Kenya, there were traces of a recent expansion and a bottleneck. Equilibrium was also rejected by two of the eight tests for both A. arabiensis populations; the departure from equilibrium was consistent with an expansion. These multiple-locus tests detected a genomewide effect and therefore a demographic event rather than a locus-specific effect, as would be caused by selection. Disequilibrium due to a recent expansion in these species implies that rates of gene flow, as inferred from differentiation indices, are overestimates as they include a historical component. We argue that the same effect applies to the majority of pest species due to the correlation of their demography with that of humans.

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J Trop Pediatr 2001 Jun;47(3):165-9Comparison of chloroquine with artesunate in the treatment of cerebral malaria in Ghanaian children.

Goka BQ, Adabayeri V, Ofori-Adjei E, Quarshie B, Asare-Odei G, Akanmori BD, Kurtzhals J, Ofori-Adjei D, Neequaye J.

Department of Child Health, Korle Bu Teaching Hospital, Accra, Ghana.

Despite previously reported chloroquine-resistant forms of PF falciparum in Ghana, chloroquine remains the drug of choice in severe malaria. Artemisinin derivatives have been shown to be effective against chloroquine-resistant strains in other endemic areas. This open randomized study was conducted to compare the efficacy of chloroquine and artesunate in the treatment of childhood cerebral malaria. Out of 82 subjects that fulfilled the inclusion criteria, 36 were randomized to receive chloroquine and 46 to receive artemisinin. Blantyre coma scores, temperature and parasitaemia were monitored. Mortality and neurological deficits were documented. There was no difference in mortality rates (chloroquine, 16.7 per cent; artesunate, 21.7 per cent; p = 0.6), neurological deficit at day 14 (chloroquine, 0 per cent; artesunate, 4.3 per cent; p = 0.3), resolution of fever (p = 0.55), and coma recovery time (p = 0.8), between the two groups. The results suggest that syrup chloroquine and intramuscular/oral artesunate currently give comparable clinical responses in the treatment of cerebral malaria in Ghana. Possible reasons for this are discussed, and suggestions are made for future antimalarial drug policy.