EHP Library Malaria Bulletin, Jan 19 – Feb 6, 2001

Full-text Reports/Articles

Proyecto Vigia in Peru

Libro Impacto Económico de la Malaria en el Perú, 2000. (Will soon be available in English also)

Política Nacional de Medicamentos para el Control de la Malaria en el Perú.

Resistencia del Plasmodium Falciparum a Medicamentos Antimaláricos
en el Perú.

Evaluación del Uso de una Prueba Rápida Inmunocromatográfica por
promotores de salud para el diagnóstico de Malaria en Areas Rurales
de la Amazonía Peruana, 1999.

Social Sciences and Malaria

 SOC. SCI. MED. 2001,  52/6 (885-909)

Private practitioners and their role in the resurgence of malaria inMumbai (Bombay) and Navi Mumbai (New Bombay), India: serving the affected or aiding an epidemic?

Kamat V.R., V.R. Kamat, Department of Anthropology, Geoscience Building, Emory,  University, Atlanta, GA 30322 United States

The increased emphasis on privatization of the health care sector in many developing countries by international financial institutions and national  governments expects an expanding role for private health care practitioners in the management of major communicable diseases such as tuberculosis, malaria, acute respiratory infections (ARIs) and sexually transmitted diseases (STDs). Largely unexamined in the Indian context, however, is the socio-cultural context, the micro-level political environment in which private practitioners carry out their activities, and the quality of care they provide to their patients. Examining these aspects is significant given the impressive growth of the country’s private health sector during the past decade. This paper reports the results of an ethnographic study carried out in Mumbai (Bombay) and Navi Mumbai (New Bombay), India on private general practitioners (GPs) and their role in the management of malaria at a time when these two neighboring cities were in the midst of the worst malaria epidemic in over 60 years.

Described are the characteristics of a sample of 48 private practitioners from the two cities, and their clinics. This is followed by a discussion of the data gathered through untructured interviews with practitioners and patients, and complemented by observational data on doctor-patient encounters gathered at 16 clinics over a 9-month period. The findings of the study suggest that many practitioners in Mumbai and Navi Mumbai were poorly qualified and did not play a supportive role in the two cities’ public health departments to bring the epidemic under control. The majority of the practitioners adopted diagnostic and treatment practices that were not consistent with the guidelines laid down by WHO and India’s National Malaria Eradication Programme. Very few practitioners, especially those practicing in low-income areas, relied on a peripheral blood-smear test to make a diagnosis. Practitioners whose clientele was mostly the poor commonly resorted to giving one-day treatment to febrile patients that included injectable antimalarials and broad spectrum antibiotics. Such practitioners justified their mode of diagnosis and treatment by asserting that they were only responding to the demands placed on them by their patients who could not afford a blood-smear test or a full prescription.

The paper argues that practitioners who acquiesced to patient demands were at once exacerbating the health problems of their patients and jeopardizing the prospects for the epidemic to be brought under control. Driven primarily by the need to retain the patronage of patients and maintain one’s popularity in a highly competitive health arena, many providers practiced medicine that was unethical and dangerous. The paper concludes by discussing the ramifications of this study for malaria control in Mumbai and Navi Mumbai, and highlights a few salient health policy issues concerning the growth of the private health sector in India and its regulation. Copyright (c) 2001.

PubMed, January 19 – February 2, 2001

Eur J Clin Pharmacol 2000 Nov;56(8):561-6

Use of saliva and capillary blood samples as substitutes for venous blood sampling in pharmacokinetic investigations of artemisinin.
Gordi T, Hai TN, Hoai NM, Thyberg M, Ashton M

Division of Biopharmaceutics and Pharmacokinetics, Uppsala University, Box 580, S-75123 Uppsala, Sweden.

OBJECTIVES: Artemisinin concentrations in venous plasma, capillary plasma and saliva were compared. METHODS: Eighteen Vietnamese adults with uncomplicated falciparum malaria were treated with artemisinin. Saliva, capillary and venous plasma were sampled and analysed for artemisinin using high-performance liquid chromatography with an ultraviolet detector (HPLC-UV). RESULTS: Artemisinin capillary plasma concentrations were highly correlated to its venous plasma levels (correlation coefficient r = 0.92). Capillary/venous concentration ratios were significantly higher than unity at 30 min and 60 min after drug intake, indicating an arterial-venous concentration difference. Artemisinin unbound fraction in plasma averaged 0.14 (SD = 0.03) and was independent of drug concentration (114-1001 ng/ml). Artemisinin concentrations in saliva were comparable to its unbound levels in plasma. Saliva levels were more highly correlated to unbound capillary plasma (r = 0.85) than to unbound venous plasma concentrations (r = 0.77). No statistically significant differences were found between the saliva, unbound venous and unbound capillary area under the curve (AUC) values. CONCLUSIONS: Capillary plasma or saliva may replace venous plasma in pharmacokinetic investigations of artemisinin. Due to the ease of collection and handling, saliva sampling can be a simple approach in field studies of artemisinin, although the lower saliva concentrations require more sensitive analytical methods.

Mil Med 2000 Dec;165(12):897-902

Malaria in the Americas: a model of reemergence.
Butler WP, Roberts DR

U.S. Air Force School of Aerospace Medicine, Brooks Air Force Base, TX, USA.

Malaria in the Americas is a reemerging health issue. In 1969, the World Health Organization shifted policy from malaria eradication to malaria control. With this shift, vector control (house spraying with dichlorodiphenyltrichloroethane [DDT]) was deemphasized. Since that time, house spray rates have decreased and malaria rates have increased. Using malaria data collected since 1959 by the Pan American Health Organization, this relationship was examined with an ecological regression model. Malaria control was found to be a function of policy, disease burden, and vector control (R2 = 0.75, p < 0.001). Policy must address both disease burden and vector control. Treatment of disease burden is unquestioned; however, vector control is debated. An argument for the judicious and enlightened resumption of house spraying with DDT is presented.

Environ Manage 2001 Mar;27(3):463-476

Analysis of Socioeconomic and Environmental Impacts of Waste Stabilization Pond and Unrestricted Wastewater Irrigation: Interface with Maintenance.
Agunwamba JC

Department of Civil Engineering, University of Nigeria, Nsukka, Nigeria

The effluent from the waste stabilization ponds (WSPs) of the University of Nigeria, Nsukka Campus, is used for irrigation by poor rural farmers. There has been fear that the poorly maintained WSPs and the reuse practices are contributing to environmental degradation and health hazards. In this study the environmental and socioeconomic impacts of the WSPs and reuse were evaluated based on data collected from questionnaires and the literature. The engineering and agricultural properties of soil in the irrigated and nonirrigated areas were compared. Comparison of the health status of the farmers and nonfarmers, of consumers of crops irrigated with wastewater and nonconsumers was performed using Student’s t test and the z-score test. The occurrences of diarrhea, typhoid fever, and malaria among the various groups were used as indices. Analyses show that the health status of the farmers and consumers is poorer than those of nonfarmers and nonconsumers at the 5% level of significance. Vegetable cultivation using WSP effluent is a means of sustenance to the farmers and provides an affordable means of satisfying their nutritional deficiencies. However, the poorly maintained WSPs create odor and mosquito nuisances, trap and destroy livestock, and flood nearby compounds with waste debris. At both 1% and 5% levels of significance, communities around the ponds (<300 m) suffer malaria more frequently than those who live far away (>/=300 m). Cost-benefit analysis argues in favor of improvement of WSP management and irrigation reuse of wastewater. Dredging of the ponds, training workers and farmers, and adopting appropriate maintenance and monitoring strategies will greatly enhance the socioeconomic status of the urban poor farmers.

Clin Microbiol Rev 2001 Jan;14(1):208-226

Current Status of Malaria and Potential for Control.
Phillips RS

Division of Infection and Immunity, University of Glasgow, Glasgow G12 8QQ, United Kingdom.

Malaria remains one of the world’s worst health problems with 1.5 to 2.7 million deaths annually; these deaths are primarily among children under 5 years of age and pregnant women in sub-Saharan Africa. Of significance, more people are dying from malaria today than 30 years ago. This review considers the factors which have contributed to this gloomy picture, including those which relate to the vector, the female anopheline mosquito; to human activity such as creating new mosquito breeding sites, the impact of increased numbers of people, and how their migratory behavior can increase the incidence and spread of malaria; and the problems of drug resistance by the parasites to almost all currently available antimalarial drugs. In a selective manner, this review describes what is being done to ameliorate this situation both in terms of applying existing methods in a useful or even crucial role in control and prevention and in terms of new additions to the antimalarial armory that are being developed. Topics covered include biological control of mosquitoes, the use of insecticide-impregnated bed nets, transgenic mosquitoes manipulated for resistance to malaria parasites, old and new antimalarial drugs, drug resistance and how best to maintain the useful life of antimalarials, immunity to malaria and the search for antimalarial vaccines, and the malaria genome project and the potential benefits to accrue from it.

Genetica 2000;108(1):73-80

Chromosome differentiated populations of Anopheles cruzii: evidence for a third sibling species.
Ramirez CC, Dessen EM

Departamento de Biologia, Instituto de Biociencias, Universidade de Sao Paulo, Brazil.

Anopheles cruzii is the most common species of mosquito in Southeast Brazil and a vector of human and monkey malaria. The banding pattern of the ovarian polytene chromosomes and the frequencies of paracentric inversions of individuals from two populations were studied. A new sequence of bands on the sex chromosome, defined as form C, was disclosed. In both populations where forms A (considered as standard) and C are sympatric no heterozygotes were detected. A sequence of events that could account for the observed changes in the banding sequences of the X chromosome forms was proposed. The frequencies of 22 paracentric inversions were used to assess panmixia and the results indicated the presence of two distinct genetic pools in each population. We consider these results as evidence of another sibling species in the taxon cruzii, characterized by a distinctive form of the X chromosome and provisionally designated Anopheles cruzii species C.

Indian J Med Sci 2000 Aug;54(8):325-9

Recurrent malaria–an enigma?
Adhikari P

Kasturba Medical College, Mangalore 575001.

Management of recurrent malaria has to be individualised. A careful history, details of the drugs received, family history, laboratory evaluation will definitely help us in arriving at a reasonable diagnosis. For the future, genotyping, PCR testing and gamma interfiron levels may help us in identifying causes for recurrences.

Mem Inst Oswaldo Cruz 2000;95 Suppl 1:59-62

Natural immunoglobulins (contribution to a debate on biomedical education).
Vaz NM

Departamento de Bioquimica e Imunologia, ICB, Universidade Federal de Minas Gerais, Caixa Postal 486, 30161-970 Belo Horizonte, MG, Brasil. Email: [email protected]

Immunology has contributed to biomedical education in many important ways since the creation of scientific medicine in the last quarter of the 19th century. Today, immunology is a major area of biomedical research. Nevertheless, there are many basic problems unresolved in immunological activities and phenomena. Solving these problems is probably necessary to devise predictable and safe ways to produce new vaccines, treat allergy and autoimmune diseases and perform safe transplants. This challenge involves not only technical developments but also changes in attitude, of which the most fundamental is to abandon the traditional stimulus-response perspective in favor of more “systemic” views. Describing immunological activities as the operation of a complex multiconnected network, raises biological and epistemological issues not usually dealt with in biomedical education. Here we point to one example of systemic approaches. A new form of immunoblot (Panama blot), by which the reaction of natural immunoglobulins with complex protein mixtures may be analyzed by a special software and multivariate statistics, has been recently used to characterize human autoimmune diseases. Our preliminary data show that Panama blots can also be used to characterize global (systemic) immunological changes in chronic human parasitic diseases, such as malaria and schistosomiasis mansoni, that correlate with the clinical status.

Ann Clin Psychiatry 2000 Dec;12(4):197-203

The best possible means of benefiting the incurable: Walter Bruetsch and the malaria treatment of paresis.
King LJ

Department of Psychiatry, Indiana University, School of Medicine, Indianapolis, USA.

The first effective treatment for a specific psychiatric disorder was not developed until the early 20th century. The promise of discovery of causes of and cures for specific diseases had come with the development of laboratory science, especially the study of infectious diseases, in the last half of the 19th century. The introduction of malaria treatment of paresis in the 1920s was a landmark in psychiatry and was possible because, in this particular disorder, the knowledge gained from the study of infectious disease could be applied to the treatment of a psychiatric disease that had resulted from an earlier infection.

Expert Opin Investig Drugs 1999 Dec;8(12):2141-2158

The therapeutic potential of iron chelators.
Richardson DR

Department of Medicine, University of Queensland, Clinical Sciences Building Floor C, Royal Brisbane Hospital, Brisbane, Australia. Email: [email protected]

In recent years there has been much interest in the development of iron (Fe) chelators for treatment of a number of clinical conditions in addition to beta-thalassaemia. These include cancer, anthracycline-mediated cardiotoxicity, malaria, AIDS and the severe neurodegenerative disease, Friedreich’s ataxia. In this review I will discuss the most recent advances achieved in the potential treatment of these conditions using Fe chelators.

Clin Diagn Lab Immunol 2001 Jan;8(1):14-20

Naturally Acquired Antibody Responses to the C-Terminal Region of Merozoite Surface Protein 1 of Plasmodium vivax in Korea.
Park JW, Moon SH, Yeom JS, Lim KJ, Sohn MJ, Jung WC, Cho YJ, Jeon KW, Ju W, Ki CS, Oh MD, Choe K

Korean Armed Forces Central Medical Research Institute, Yusong-gu, Daejeon, Chongno-gu, Seoul 110-744, Republic of Korea.

We expressed a protein in Saccharomyces cerevisiae in order to evaluate the humoral immune responses to the C-terminal region of the merozoite surface protein 1 of Plasmodium vivax. This protein (Pv200(18)) had a molecular mass of 18 kDa and was reactive with the sera of individuals with patent vivax malaria on immunoblotting analysis. The levels of immunoglobulin M (IgM) and IgG antibodies against Pv200(18) were measured in 421 patients with vivax malaria (patient group), 528 healthy individuals from areas of nonendemicity (control group 1), and 470 healthy individuals from areas of endemicity (control group 2), using the indirect enzyme-linked immunosorbent assay (ELISA) method. To study the longevity of the antibodies, 20 subjects from the patient group were also tested for the antibody levels once a month for 1 year. When the cutoff values for seropositivity were determined as the mean + 3 x standard deviation of the antibody levels in control group 1, both IgG and IgM antibody levels were negative in 98.5% (465 of 472) of control group 2. The IgG and IgM antibodies were positive in 88.1% (371 of 421) and 94.5% (398 of 421) of the patient group, respectively. The IgM antibody became negative 2 to 4 months after the onset of symptoms, whereas the IgG antibody usually remained positive for more than 5 months. In conclusion, indirect ELISA using Pv200(18) expressed in S. cerevisiae may be a useful diagnostic method for vivax malaria.

Korean J Parasitol 2000 Dec;38(4):263

Comparative study on longevity of Anopheles sinensis in malarious and non-malarious areas in Korea.
Ree HI, Hwang UW

Institute of Tropical Medicine and Department of Parasitology, Yonsei University College of Medicine, Seoul 120-752, Korea. Email: [email protected]

An outbreak of vivax malaria has been occurring in northern part of Kyonggi-do and north-western part of Kangwon-do, where are located near the demilitarized zone, since 1993. For understanding of epidemiological features of malaria, the probability of daily survival of Anopheles sinensis, the vector species of malaria was compared in malarious and non-malarious areas in July-August, 2000. Total 915 females collected at three locations in malarious areas were dissected for ovaries, and 64.6% of the parous rate was found. Total 758 females collected at three locations in non-malarious areas were dissected, and 57.8% of the parous rate was observed. It was estimated from the parous rates that the probability of daily survival of An. sinensis females was 0.864 in malarious areas and 0.850 in non-malarious areas, which was not significantly different.

J Biochem (Tokyo) 2001 Jan 1;129(1):101-105

Purification and Properties of Recombinant Plasmodium falciparum S-Adenosyl-L-Homocysteine Hydrolase.
Nakanishi M, Iwata A, Yatome C, Kitade Y

Laboratory of Molecular Biochemistry, Department of Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido 1-1, Gifu 501-1193, Japan. Email: [email protected]

Recombinant S-adenosyl-L-homocysteine (SAH) hydrolase of the malaria parasite Plasmodium falciparum was expressed in Escherichia coli, purified to homogeneity and characterized. Comparison of the malaria parasite SAH hydrolase with that derived from the human gene indicated marked differences in k(cat) values. The values of both forward and reverse reactions of P. falciparum SAH hydrolase are more than 21-fold smaller than those of the human enzyme. K(m) values of the parasite and human SAH enzymes are 1.2 and 7.8 ?M, respectively. On the other hand, IC(50) values of neplanocin A, a strong inhibitor of SAH hydrolase and a growth inhibitor of P. falciparum, are 101 nM for the parasite enzyme and 47 nM for human enzyme. P. falciparum SAH hydrolase has been thought to be a target for a chemotherapeutic agent against malaria. This study may make it possible to develop a specific inhibitor for the parasite SAH hydrolase.

Acta Crystallogr D Biol Crystallogr 2001 Jan 1;57(Pt 1):134-136

Crystallization of agGST1-6, a recombinant glutathione S-transferase from a DDT-resistant strain of Anopheles gambiae.
Roberts PH, Zhou X, Holmes AM, Ranson H, Small G, Hemingway J, Ng JD, Chen L, Meehan EJ

Laboratory for Structural Biology, University of Alabama in Huntsville, MSB 203C, Huntsville, AL 35899, USA.

Glutathione S-transferases (GSTs) belong to a family of detoxification enzymes that conjugate glutathione to various xenobiotics, thus facilitating their expulsion from the cell. GST activity is elevated in many insecticide-resistant insects, including the DDT-resistant malaria vector Anopheles gambiae. Crystals of the recombinant form of a GST from A. gambiae, agGST1-6, have been grown in at least five different crystal forms, with a broad range of diffraction resolution limits. A complete 2.0 A data set has been collected on a C-centered orthorhombic crystal form with unit-cell parameters a = 99.0, b = 199.4, c = 89.6 A. A search for heavy-atom derivatives has been initiated, along with phase-determination efforts by molecular replacement.

Mol Phylogenet Evol 2000 Dec;17(3):430-436

A Phylogenetic Study of the Anopheles punctulatus Group of Malaria Vectors Comparing rDNA Sequence Alignments Derived from the Mitochondrial and Nuclear Small Ribosomal Subunits.
Beebe NW, Cooper RD, Morrison DA, Ellis JT

Molecular Parasitology Unit, University of Technology, Sydney, New South Wales, 2065, Australia

A phylogenetic study of the members of the Anopheles punctulatus group was performed using structural and similarity-based DNA sequence alignments of the small ribosomal subunit (SSU) from both the nuclear and the mitochondrial genomes. The mitochondrial SSU gene (12S, approximately 650 bp) proved to be highly restricted by its secondary structure and displayed little informative sequence variation. Consequently, it was considered unsuitable for a phylogenetic study of these closely related mosquito species. A structural alignment of the nuclear ribosomal DNA SSU (18S, approximately 2000 bp) proved to be more informative than similarity-based alignments. Analyses showed the A. punctulatus group to be monophyletic with two major clades; a Farauti clade containing members displaying an all-black-scaled proboscis (A. farauti 1-3 and 5-7) and the Punctulatus clade containing members displaying extensive white scaling on the apical half of the proboscis (A. farauti 4, A. punctulatus, and An. sp. near punctulatus). Anopheles koliensis was positioned basal to the Farauti clade. Copyright 2000 Academic Press.

Trans R Soc Trop Med Hyg 2000 Sep;94(5):557-62

Immune response to Plasmodium falciparum liver stage antigen-1: geographical variations within Central Africa and their relationship with protection from clinical malaria.
Migot-Nabias F, Deloron P, Ringwald P, Dubois B, Mayombo J, Minh TN, Fievet N, Millet P, Luty A

Centre International de Recherches Medicales de Franceville (CIRMF), Gabon. Email: [email protected]

Two populations of schoolchildren from Gabon and Cameroon were tested in 1995 for their immunological reactivity to synthetic peptides (LSA-Rep, LSA-J and LSA-CTL) from Plasmodium falciparum liver stage antigen-1 (LSA-1). The prevalence and levels of both cellular (lymphocyte proliferation, tumour necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma), and interleukin-10 (IL-10)) and humoral (immunoglobulin G) responses were determined. Protection from clinical malaria, determined after a prospective 1 year study in both sites, was associated with elevated proliferative responses to LSA-Rep and LSA-CTL in the Gabonese children, as well as with higher antibody levels to both schizont extract and LSA-Rep. The prevalence of peptide-stimulated TNF-alpha secretion was higher in the Cameroonian group, but higher levels of antibodies to LSA-Rep and LSA-J were found in the Gabonese children. The immunological differences observed between children in the 2 study sites are discussed in the context of both epidemiological and individual host factors.

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