Social Sciences/Environmental Management

Laboratory and field comparisons of pyriproxyfen, polystyrene beads and other larvicidal methods against malaria vectors in Sri Lanka.

Yapabandara AM, Curtis CF.

Regional Office, Anti-Malaria Campaign, Matale, Sri Lanka

Hand-dug gem pits are important breeding sites for larvae of malaria vectors in Sri Lanka. Therefore, studies were carried out to help to select an effective, economic and convenient method that could be used to control malaria vector mosquito breeding in gem pits in a mining area. The effectiveness of four types of floating layers of polystyrene was compared in the laboratory and it was found that 2 mm expanded beads were the most effective for suffocating Anopheles larvae and pupae. The insect growth regulator, pyriproxyfen at dosages of 0.01 and 0.1 mg/l were tested in the laboratory and complete inhibition of emergence was found at both concentrations. A small-scale field trial was carried out for over a year to assess the efficacy of two concentrations of pyriproxyfen, 2 mm diameter expanded polystyrene beads, temephos, used engine oil and filling pits with soil. Pyriproxyfen only required re-application twice a year, whereas temephos or oil require 12 applications per year. Due to re-excavation by gem miners, polystyrene beads and filling of pits were not as permanent solutions as was expected. Calculations based on all available data showed that two annual treatments with pyriproxyfen at 0.01 mg/l would be the most cost-effective method with oil only slightly more expensive. However, the reduced required frequency for visiting every pit made the pyriproxyfen method the one of choice. The same low concentration of pyriproxyfen also effectively inhibited emergence of adults from river-bed pools.

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Nature 2002 Feb 7;415(6872):680-5

The economic and social burden of malaria.

Sachs J, Malaney P.

Center for International Development, John F. Kennedy School of Government, Harvard University, 79 John F. Kennedy St., Cambridge, Massachusetts 02138, USA.

Where malaria prospers most, human societies have prospered least. The global distribution of per-capita gross domestic product shows a striking correlation between malaria and poverty, and malaria-endemic countries also have lower rates of economic growth. There are multiple channels by which malaria impedes development, including effects on fertility, population growth, saving and investment, worker productivity, absenteeism, premature mortality and medical costs.

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Lancet 2002 Feb 2;359(9304):435-8

GAVI, the first steps: lessons for the Global Fund.

Brugha R, Starling M, Walt G.

Health Policy Unit, Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK. 
Email: [email protected]

The Global Alliance for Vaccines and Immunization (GAVI) is seen as a model for the new Global Fund to Fight AIDS, Tuberculosis and Malaria, to be launched early in 2002. We did an assessment in four African countries to report the experiences of ministries of health and their partners in applying to GAVI for funds to strengthen health systems and for new vaccines. Countries welcomed the introduction of hepatitis B vaccine, safe injection equipment, and the financial support to strengthen immunisation programmes. All reported that the pace of the application process was too rapid. District visits revealed low staffing levels, insufficient transport and fuel, poorly functioning cold chains, and infrequent supervision. Information systems were unreliable, which will be an obstacle to GAVI when monitoring and rewarding improvements in immunisation coverage. Also, the high cost of expensive new vaccines will be difficult to sustain if GAVI funding stops at the end of its 5 year commitment. Our study suggests that applications for support and planning for AIDS, tuberculosis, and malaria control under the new Global Fund, will be more complex and demanding on already over-stretched ministries of health. Further, the rapid onset of activities, coupled with uncertainty about the time-scale of donor commitment, could be problematic. A limited and carefully assessed set of initial activities, focusing on where and how to strengthen existing country systems, is more likely to be successful and could provide useful models for scaling-up to larger programmes in different contexts.

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Trop Med Int Health 2002 Feb;7(2):187-96

Examining out-of-pocket expenditure on health care in Nouna, Burkina Faso: implications for health policy.

Mugisha F, Kouyate B, Gbangou A, Sauerborn R.

Department of Tropical Hygiene and Public Health, Heidelberg University, Heidelberg, Germany, Centre de Recherche en Sante de Nouna (CRSN), Nouna District, Burkina Faso.

OBJECTIVE To examine household out-of-pocket expenditure on health care, particularly malaria treatment, in rural Burkina Faso. METHOD Comprehensive analysis of out-of-pocket expenditure on health care through a descriptive analysis and a second, multivariate analysis using the Tobit model with emphasis on malaria, based on 800 urban and rural households in Nouna health district. RESULTS Households will spend less on malaria, either in or outside the health facility, if given the choice to do so, because they feel confident to self-treat malaria. Seeking health care from a qualified health worker incurs more out-of-pocket expenditure than self-treatment and traditional healers, and if necessary, households sell off assets to offset the expenditure. More than 80% of household out-of-pocket expenditure is allocated to drugs. CONCLUSION This has policy implications for malaria control and the Roll Back Malaria Initiative. Communities need to be educated on the risks of malaria complications and the potential risk of inappropriate diagnosis and treatment. Drug or health services pricing policy needs to create an incentive to use the health services. In the fight against malaria, building alliances between households, traditional healers and health workers is essential.

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Trop Med Int Health 2002 Feb;7(2):149-158

Socially marketed insecticide-treated nets improve malaria and anaemia in pregnancy in southern Tanzania.

Marchant T, Schellenberg JA, Edgar T, Nathan R, Abdulla S, Mukasa O, Mponda H, Lengeler C.

Ifakara Health Research and Development Centre, Ifakara, Tanzania, Swiss Tropical Institute, Basel, Switzerland.

OBJECTIVES To study the uptake of socially marketed insecticide-treated nets (ITNs) and their impact on malaria and anaemia in pregnancy; and to report on a discount voucher system which aimed to increase coverage in pregnancy.METHODS A 12-month cross-sectional study of women in the second or third trimester of pregnancy. ITN use and other factors were assessed by questionnaire and a blood sample taken for malaria parasitaemia and anaemia. ‘Non-users’ of ITNs included both women not using any net and women using untreated nets.RESULTS Fifty three per cent of pregnant women used ITNs. Women aged 15–19, primigravidae, unmarried women, and those with no access to cash had the lowest ITN use. Fewer ITN users were positive for malaria than ITN non-users (25 vs. 33%: P=0.06), and the protective efficacy (PE) for parasitaemia was 23% (CI 2–41). Multiparous ITN users had a twofold decrease in parasite density compared with multiparous non-ITN users (625parasites/[mu]l vs. 1173 parasited/[mu]l: P=0.01). Fewer ITN users were anaemic (Hb < 11 g/dl) than ITN non-users (72 vs. 82%: P=0.01). ITNs had a PE of 12% (CI 2–21) against mild anaemia and a PE of 38% (CI 4–60) against severe anaemia (Hb < 8 g/dl). There was a trend in the prevalence of severe, mild and no anaemia, and of high density, low density and no malaria infection by ITN status. Recently treated nets were most effective at preventing malaria and anaemia (prevalence of mild anaemia was 68% compared with 82% for those without nets (P=0.002); prevalence of malaria was 22% compared with 33% for those without nets (P=0.02). Knowledge and reported use of the discount voucher system were low. Further qualitative research is ongoing.CONCLUSIONS A modest impact of ITNs on pregnancy malaria and anaemia was shown in our high malaria transmission setting. The development of ITN programmes for malaria control should include pregnant women as a specific target group.

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PubMed

Science 2002 Feb 15;295(5558):1311-1314  

A Class of Potent Antimalarials and Their Specific Accumulation in Infected Erythrocytes.

Wengelnik K, Vidal V, Ancelin ML, Cathiard AM, Morgat JL, Kocken CH, Calas M, Herrera S, Thomas AW, Vial HJ.

CNRS UMR 5539, CP 107, CNRS UMR 5810, CP 22, Universite Montpellier II, Place E. Bataillon, 34095 Montpellier Cedex 5, France., CRBA CNRS UMR 5473, Universite Montpellier I, Faculte de Pharmacie, 15 Av. Charles Flahault, 34060 Montpellier, France., Department of Parasitology, Biomedical Primate Research Centre, Postbox 3306, 2280 GH Rijswijk, Netherlands., Fundacion Centro de Primates, Universidad del Valle, Cali, Colombia.

During asexual development within erythrocytes, malaria parasites synthesize considerable amounts of membrane. This activity provides an attractive target for chemotherapy because it is absent from mature erythrocytes. We found that compounds that inhibit phosphatidylcholine biosynthesis de novo from choline were potent antimalarial drugs. The lead compound, G25, potently inhibited in vitro growth of the human malaria parasites Plasmodium falciparum and P. vivax and was 1000-fold less toxic to mammalian cell lines. A radioactive derivative specifically accumulated in infected erythrocytes to levels several hundredfold higher than in the surrounding medium, and very low dose G25 therapy completely cured monkeys infected with P. falciparum and P. cynomolgi.

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EMBO J 2002 Feb 15;21(4):815-824

A central role for Plasmodium falciparum subtelomeric regions in spatial positioning and telomere length regulation.

Figueiredo LM, Freitas-Junior LH, Bottius E, Olivo-Marin JC, Scherf A.

Unite de Biologie des Interactions Hote-Parasite, CNRS URA 1960, Institut Pasteur and Laboratoire d’Analyse d’Images Quantitative, URA CNRS 1947, Institut Pasteur, 25 rue du Dr Roux, F-75724 Paris Cedex 15, France Present address: Gen Odysse, Les Ulis, F-91974 Courtaboeuf Cedex, France Corresponding author Email: [email protected]

In the protozoan malaria parasite, Plasmodium falciparum, the telomere-associated sequences (TASs) of the 14 linear chromosomes display a similar higher order organization and form clusters of four to seven telomeres localized at the nuclear periphery. Experimental evidence has shown that the physical tethering of chromosome ends enhances the ectopic recombination between gene families involved in antigenic variation and parasite sequestration. Using FISH analysis, we observed that chromosome ends lacking the subtelomeric region are usually delocalized from telomere clusters, but still remain at the nuclear periphery. This indicates that subtelomeric DNA is necessary for cluster formation but is not essential for peripheral positioning. Intriguingly, these truncated chromosomes have unusually long telomeric tracts (up to three times longer than average length), showing that TASs play a role in telomere length regulation. On these chromosomes, the newly formed telomere frequently extends from truncated genes leading, in some cases, to the transcription of telomeric DNA. The implications of both subtelomeric gene expression and nuclear architecture in the virulence of this serious human pathogen are discussed.

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Bull Soc Pathol Exot 2001 Nov;94(4):353-7

Malaria has long constituted a major public health problem for French Guyana,

[Article in French]

Claustre J, Venturin C, Nadire M, Fauran P.

Malaria has long constituted a major public health problem for French Guyana, limiting its demographic and economic development. From 1949 to 1960, due to chemoprophylaxis and DDT spraying in houses, the number of malaria cases decreased markedly. After 1975, important migratory movements contributed to increasing the incidence of malaria. In 1989, numerous cases were observed when some 500 immigrants settled in a formerly uninhabited area, known as Cabassou BP 134. It is located 7 km (S-E) from the main city of Cayenne and bordered by secondary forest and swamps. The entomological study initiated in 1990 included weekly biting-landing catches (3 hours) on human bait in houses from dusk onwards as well as locating breeding places around the settlement to collect larvae by dipping. Anopheles specimens were identified and the females dissected to detect infections by Plasmodium and also to determine the rate of parous specimens. Control measures included deltamethrin (15 mg/m2) and DDT (2 g/m2) spraying, every four months, of interior walls and thermal fogging of naled around the houses. Cold ULV aerosol of fenitrothion (500 ml/ha) was also used to treat the swamp borders. In April 1990, a health education programme was begun and in June, 288 impregnated bednets (deltamethrin 15 mg/m2) were treated. From 1990 to 1998, 1,588 (498 larvae + 1090 adults) Anopheles (Nyssorhynchus) were collected: An. aquasalis 797 (311 L + 486 A). An. braziliensis 139 (87 L + 52 A). An. darlingi 652 (100 L + 552 A). No infected female was found among the 710 dissected. The number of malaria cases decreased abruptly in the fall of 1990 when An. darlingi disappeared and only one case due to P. vivax was detected between 1995 and 1998. An. darlingi (parous rate = 72%) appears to be the main if not the sole vector of malaria in this locality. As in the past, a focus of malaria appears when immigrants from endemic countries settle in a formerly uninhabited place where An. darlingi are breeding.

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Curr Opin Hematol 2002 Mar;9(2):140-5

Hydrolysis of erythrocyte proteins by proteases of malaria parasites.

Rosenthal PJ.

Department of Medicine, University of California, San Francisco, California, USA.

During the intraerythrocytic phase of the life cycle, malaria parasites hydrolyze host proteins. Hemoglobin is processed into individual amino acids, which are used for parasite protein synthesis. Erythrocyte cytoskeletal proteins are cleaved during erythrocyte invasion and rupture. A number of plasmodial proteases that appear to be responsible for key cleavages of host proteins have recently been characterized. Hemoglobin hydrolysis appears to be mediated by acid cysteine, aspartic, and metalloproteases, and then a neutral aminopeptidase. Cysteine and aspartic proteases that hydrolyze hemoglobin can also cleave host cytoskeletal proteins, and these and additional proteases likely cleave the cytoskeleton to mediate erythrocyte rupture and invasion. Various protease inhibitors block parasite development, suggesting that key proteases may be appropriate chemotherapeutic targets. Recent advances in the characterization of plasmodial proteases should facilitate the analysis of the specific roles of these enzymes and expedite the progress of drug discovery efforts directed against them.

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Bioorg Med Chem Lett 2002 Feb 25;12(4):539-42

New anti-Malarial compounds from database searching.

Griffith R, Chanphen R, Leach SP, Keller PA.

School of Biological and Chemical Sciences, University of Newcastle, 2308, Callaghan, NSW, Australia

In a serendipitous result, pharmacophores generated for the database searching for new non-nucleoside inhibitors of the HIV-1 reverse transcriptase enzyme unearthed 12 new lead compounds which were active against the Plasmodium falciparum strain of malaria.

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Biochemistry 2002 Feb 19;41(7):2273-2280

Identification and Characterization of Allophenylnorstatine-Based Inhibitors of Plasmepsin II, an Antimalarial Target.

Nezami A, Luque I, Kimura T, Kiso Y, Freire E.

Department of Biology and The Johns Hopkins Malaria Research Institute, The Johns Hopkins University, Baltimore, Maryland 21218, and Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.

Plasmepsin II is a key enzyme in the life cycle of the Plasmodium parasites responsible for malaria, a disease that afflicts more than 300 million individuals annually. Since plasmepsin II inhibition leads to starvation of the parasite, it has been acknowledged as an important target for the development of new antimalarials. In this paper, we identify and characterize high-affinity inhibitors of plasmepsin II based upon the allophenylnorstatine scaffold. The best compound, KNI-727, inhibits plasmepsin II with a K(i) of 70 nM and a 22-fold selectivity with respect to the highly homologous human enzyme cathepsin D. KNI-727 binds to plasmepsin II in a process favored both enthalpically and entropically. At 25 e, Greece.nd pheromone-binding proteins, raises the possibility that the D7r-encoded proteins may bind and/or carry small hydrophobic ligands.arous ITN users had a twofold decrease in parasite density compared with multiparous non-ITN users (625parasites/[C, the binding enthalpy ([Delta]H) is [minus sign]4.4 kcal/mol and the entropic contribution ([minus sign]T[Delta]S) to the Gibbs energy is [minus sign]5.56 kcal/mol. Structural stability measurements of plasmepsin II were also utilized to characterize inhibitor binding. High-sensitivity differential scanning calorimetry experiments performed in the absence of inhibitors indicate that, at pH 4.0, plasmepsin II undergoes thermal denaturation at 63.3 naemia (prevalence of mild anaemia was 68% compared with 82% for those without nets (P=0.002); prevalence of malaria was 22% compared with 33% for those without nets (P=0.02). Knowledge and reported use of the discount voucher system were low. Further qualC. The structural stability of the enzyme increases with inhibitor concentration in a manner for which the binding energetics of the inhibitor can quantitatively account. The effectiveness of the best compounds in killing the malaria parasite was validated by performing cytotoxicity assays in red blood cells infected with Plasmodium falciparum. EC(50)s ranging between 6 and 10 [mu]M (3[minus sign]6 [mu]g/mL) were obtained. These experiments demonstrate the viability of the allophenylnorstatine scaffold in the design of powerful and selective plasmepsin inhibitors.

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Int J Parasitol 2002 Jan;32(1):91-8

The role of Plasmodium berghei ookinete proteins in binding to basal lamina components and transformation into oocysts.

Arrighi RB, Hurd H.

Centre for Applied Entomology and Parasitology, School of Life Sciences, Huxley Building, Keele University, Staffordshire, ST5 5BG, Keele, UK

The ookinete is a motile form of the malaria parasite that travels from the midgut lumen of the mosquito, invades the epithelial cells and settles beneath the basal lamina. The events surrounding cessation of ookinete motility and its transformation into an oocyst are poorly understood, but interaction between components of the basal lamina and the parasite surface has been implicated. Here we report that interactions occur between basal lamina constituents and ookinete proteins and that these interactions inhibit motility and are likely to be involved in transformation to an oocyst. Plasmodium berghei ookinetes bound weakly to microtitre plate wells coated with fibronectin and much more strongly to wells coated with laminin and collagen IV. A 1:1 mixture of collagen and laminin significantly enhanced binding. Binding increased with time of incubation up to 10 h and different components showed different binding profiles with time. Two parasite molecules were shown to act as ligands for basal lamina components. Western blots demonstrated that the surface molecule Pbs21 bound strongly to laminin but not to collagen IV whereas a 215 kDa molecule (possibly PbCTRP) bound to both laminin and collagen IV. Furthermore up to 90% inhibition of binding of ookinetes to collagen IV/laminin combination occurred if parasites were pre-incubated with anti-Pbs21 monoclonal antibody 13.1. Some transformation of ookinetes to oocysts occurred in wells coated with laminin or laminin/collagen IV combinations but collagen IV alone did not trigger transformation. No binding or transformation occurred in uncoated wells. Our data support the suggestion that ookinete proteins Pbs21 and a 215 kDa protein may have multiple roles including interactions with midgut basal lamina components that cause binding, inhibit motility and trigger transformation.

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Int J Parasitol 2002 Jan;32(1):81-9

Negative selection of Plasmodium falciparum reveals targeted gene deletion by double crossover recombination.

Duraisingh MT, Triglia T, Cowman AF.

The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, 3050, Melbourne, Vic., Australia

The genome sequence of Plasmodium falciparum, the causative agent of the most severe form of malaria in humans, rapidly approaches completion, but our ability to genetically manipulate this organism remains limited. Chromosomal integration has only been achieved following the prolonged maintenance of circularised episomal plasmids which selects for single crossover recombinants. It has not been possible to construct genetic deletions via double crossover recombination, presumably due to the low frequency of this event. We have used the Herpes simplex virus thymidine kinase gene and the Escherichia coli cytosine deaminase gene for negative selection of P. falciparum. Parasites were transformed with plasmids expressing the thymidine kinase and cytosine deaminase genes by positive selection for the human dihydrofolate reductase gene. Parasites expressing thymidine kinase are susceptible to the pro-drug ganciclovir while those expressing cytosine deaminase are sensitive to 5-fluorocytosine. Parental parasites were inherently resistant to these drugs. A significant ‘bystander effect’ was evident in cultures with either ganciclovir or 5-fluorocytosine. Positive and negative selection of the thymidine kinase transformants with both ganciclovir and WR99210 resulted in the selection of parasites containing a genetic deletion of the Pfrh3 gene, the first targeted double crossover deletions in P. falciparum. The use of negative selection for gene disruptions via double crossover recombination will dramatically improve our ability to analyse protein function and opens the possibility of using this strategy for a variety of gene deletion and modification experiments in the analysis of this important infectious agent.

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Am J Pathol 2002 Feb;160(2):655-666

Axonal Injury in Cerebral Malaria.

Medana IM, Day NP, Hien TT, Mai NT, Bethell D, Phu NH, Farrar J, Esiri MM, White NJ, Turner GD.

Nuffield Departments of Clinical LaboratorySciences and Medicine, andthe Department of Neuropathology, Universityof Oxford, Oxford, United Kingdom. and the Wellcome TrustResearch Unit, Cho Quan Hospital, Ho ChiMinh City, Viet Nam.

Impairment of consciousness and other signs of cerebral dysfunction are common complications of severe Plasmodium falciparum malaria. Although the majority of patients make a complete recovery a significant minority, particularly children, have sequelae. The pathological process by which P. falciparum malaria induces severe but usually reversible neurological complications has not been elucidated. Impairment of transport within nerve fibers could induce neurological dysfunction and may have the potential either to resolve or to progress to irreversible damage. [beta]-amyloid precursor protein ([beta]-APP) immunocytochemistry, quantified using digital image analysis, was used to detect defects in axonal transport in brain sections from 54 Vietnamese cases with P. falciparum malaria. The frequency and extent of [beta]-APP staining were more severe in patients with cerebral malaria than in those with no clinical cerebral involvement. [beta]-APP staining was often associated with hemorrhages and areas of demyelination, suggesting that multiple processes may be involved in neuronal injury. The age of focal axonal damage, as determined by the extent of the associated microglial response, varied considerably within tissue sections from individual patients. These findings suggest that axons are vulnerable to a broad range of cerebral insults that occur during P. falciparum malaria infection. Disruption in axonal transport may represent a final common pathway leading to neurological dysfunction in cerebral malaria.

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Philos Trans R Soc Lond B Biol Sci 2002 Jan 29;357(1417):101-7

Metabolic pathway analysis in trypanosomes and malaria parasites.

Fairlamb AH.

Division of Biological Chemistry and Molecular Microbiology, The Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, UK.

Identification of novel drug targets is required for the development of new classes of drugs to overcome drug resistance and replace less efficacious treatments. In theory, knowledge of the entire genome of a pathogen identifies every potential drug target in any given microbe. In practice, the sheer complexity and the inadequate or inaccurate annotation of genomic information makes target identification and selection somewhat more difficult. Analysis of metabolic pathways provides a useful conceptual framework for the identification of potential drug targets and also for improving our understanding of microbial responses to nutritional, chemical and other environmental stresses. A number of metabolic databases are available as tools for such analyses. The strengths and weaknesses of this approach are discussed.

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Philos Trans R Soc Lond B Biol Sci 2002 Jan 29;357(1417):55-63

Orthology between the genomes of Plasmodium falciparum and rodent malaria parasites: possible practical applications.

Waters AP.

Department of Parasitology, Leiden University Medical Centre, Postbus 9600, 2300 RC Leiden, The Netherlands.

The work of the consortium that has been formed to complete the entire sequence of the genome of a selected clone of the human malaria parasite, Plasmodium falciparum, is almost finished. Already huge tracts of the genome are available as fully assembled chromosomes or large contigs and the work of initial annotation is in an advanced state. Post-genomic research is in one sense the process of furthering the process of annotation, creating biological atlases and preliminary attempts to make global descriptions of gene transcription and proteome analysis are underway. Comparison between significant amounts of genome data from both closely, and more distantly related organisms, can facilitate the identification of genes themselves, coordinately regulated gene expression groups, gene function and genome organization. Models of malaria can fulfil these functions and in addition provide an experimental system wherein predictions can be tested and basic experimental investigations performed within numerous aspects of disease, pathology, parasite-host and parasite-vector interactions. Comparative genomics in Plasmodium has already been shown to have informative roles in the completion of annotation and the elucidation of gene function. These roles will be illustrated by example and used as the basis for a discussion of the utility of genome information and malaria models in realizing the desired product of Plasmodium genomics, the development of malaria therapies.

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Philos Trans R Soc Lond B Biol Sci 2002 Jan 29;357(1417):25-33

Functional analysis of Plasmodium falciparum merozoite antigens: implications for erythrocyte invasion and vaccine development.

Cowman AF, Baldi DL, Duraisingh M, Healer J, Mills KE, O’Donnell RA, Thompson J, Triglia T, Wickham ME, Crabb BS.

The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia.

Malaria is a major human health problem and is responsible for over 2 million deaths per year. It is caused by a number of species of the genus Plasmodium, and Plasmodium falciparum is the causative agent of the most lethal form. Consequently, the development of a vaccine against this parasite is a priority. There are a number of stages of the parasite life cycle that are being targeted for the development of vaccines. Important candidate antigens include proteins on the surface of the asexual merozoite stage, the form that invades the host erythrocyte. The development of methods to manipulate the genome of Plasmodium species has enabled the construction of gain-of-function and loss-of-function mutants and provided new strategies to analyse the role of parasite proteins. This has provided new information on the role of merozoite antigens in erythrocyte invasion and also allows new approaches to address their potential as vaccine candidates.

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Life Sci 2002 Jan 4;70(7):769-78

Simple and rapid physico-chemical methods to examine action of antimalarial drugs with hemin: its application to Artemisia annua constituents.

Bilia AR, Lazari D, Messori L, Taglioli V, Temperini C, Vincieri FF.

Department of Pharmaceutical Sciences, University of Florence, Firenze, Italy. Email: [email protected]

Malaria is a major health problem in many countries and according to an estimate of the WHO, more than 500 million infections occur per year. Artemisinin, a sesquiterpene from Artemisia annua L., has received considerable attention as a promising and potent antimalarial drug for its stage speciticity, its rather low toxicity, effectiveness against drug-resistant Plasmodium species and activity against cerebral malaria. From recent studies it seems that hemin is primarily involved in the antimalarial activity of the constituents of Artemisia annua L. Thus, the interaction of a compound with hemin may represent a crucial screening test to define its efficacy. In this study the interaction between artemisinin and hemin was investigated by UltraViolet/Visible (UV/Vis) spectrophotometry and High Performance Liquid Chromatography/Diode Array Detector/Mass Spectrometry (HPLC/DAD/MS). In addition, some flavonols isolated from Artemisia annua L. were also tested to investigate their possible role in the interaction between artemisinin and hemin. These two simple physico-chemical methods can be useful as rapid and widespread screening methods for the search of other alkylating antimalarial constituents from natural sources or for the evaluation of the activity of semisynthetic analogues of artemisinin.

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Nature 2002 Feb 7;415(6872):710-5

Satellite imagery in the study and forecast of malaria.

Rogers DJ, Randolph SE, Snow RW, Hay SI.

TALA Research Group, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.

More than 30 years ago, human beings looked back from the Moon to see the magnificent spectacle of Earth-rise. The technology that put us into space has since been used to assess the damage we are doing to our natural environment and is now being harnessed to monitor and predict diseases through space and time. Satellite sensor data promise the development of early-warning systems for diseases such as malaria, which kills between 1 and 2 million people each year.

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Nature 2002 Feb 7;415(6872):702-9

Plasmodium, human and Anopheles genomics and malaria.

Hoffman SL, Subramanian GM, Collins FH, Venter JC.

Celera Genomics, 45 West Gude Drive, Rockville, Maryland 20850, USA.

The Plasmodium spp. parasites that cause malaria are transmitted to humans by Anopheles spp. mosquitoes. Scientists have now amassed a great body of knowledge about the parasite, its mosquito vector and human host. Yet this year there will be 300-500 million new malaria infections and 1-3 million deaths caused by the disease. We believe that integrated analyses of genome sequence, DNA polymorphisms, and messenger RNA and protein expression profiles will lead to greater understanding of the molecular basis of vector-human and host-parasite interactions and provide strategies to build upon these insights to develop interventions to mitigate human morbidity and mortality from malaria.

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Nature 2002 Feb 7;415(6872):694-701

Progress and challenges for malaria vaccines.

Richie TL, Saul A.

Malaria Program, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, Maryland 20910-7500, USA.

Malaria causes much physical and economic hardship in tropical regions, particularly in communities where medical care is rudimentary. Should a vaccine be developed, it is the residents of these areas that stand to benefit the most. But the vaccine, which has been promised to be ‘just round the corner’ for many years, remains elusive. It is important to ask why this is so, when effective vaccines exist for many other infectious diseases. What are the reasons for the slow rate of progress, and what has been learned from the first clinical trials of candidate malaria vaccines? What are the remaining challenges, and what strategies can be pursued to address them?

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Nature 2002 Feb 7;415(6872):686-93

Medical need, scientific opportunity and the drive for antimalarial drugs.

Ridley RG.

Continued and sustainable improvements in antimalarial medicines through focused research and development are essential for the world’s future ability to treat and control malaria. Unfortunately, malaria is a disease of poverty, and despite a wealth of scientific knowledge there is insufficient market incentive to generate the competitive, business-driven industrial antimalarial drug research and development that is normally needed to deliver new products. Mechanisms of partnering with industry have been established to overcome this obstacle and to open up and build on scientific opportunities for improved chemotherapy in the future.

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Nature 2002 Feb 7;415(6872):673-9

The pathogenic basis of malaria.

Miller LH, Baruch DI, Marsh K, Doumbo OK.

Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Malaria is today a disease of poverty and underdeveloped countries. In Africa, mortality remains high because there is limited access to treatment in the villages. We should follow in Pasteur’s footsteps by using basic research to develop better tools for the control and cure of malaria. Insight into the complexity of malaria pathogenesis is vital for understanding the disease and will provide a major step towards controlling it. Those of us who work on pathogenesis must widen our approach and think in terms of new tools such as vaccines to reduce disease. The inability of many countries to fund expensive campaigns and antimalarial treatment requires these tools to be highly effective and affordable.

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Nature 2002 Feb 7;415(6872):670-2

Malaria in 2002.

Greenwood B, Mutabingwa T.

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.

The burden of malaria is increasing, especially in sub-Saharan Africa, because of drug and insecticide resistance and social and environmental changes. Thus, there is an urgent need for vaccines, new drugs and insecticides. Parasite, mosquito and human genome projects are helping in the search for new control tools and international donors are developing new funding mechanisms that could make them available to poor countries. But these new tools will achieve their maximum impact only if additional resources are deployed to strengthen malaria research and control communities in countries where the new tools will be used.

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J Postgrad Med 2001 Oct;47(4):240-243

In-vitro Antimalarial Activity of Azithromycin Against Chloroquine Sensitive and Chloroquine Resistant Plasmodium Falciparum.

Biswas S.

Malaria Research Centre (ICMR), 22 Sham Nath Marg, Delhi – 110 054, India. Email: [email protected]

BACKGROUND: The spread of drug resistance in Plasmodium falciparum has made the situation essential to look into new effective therapeutic agents like antibiotics. Azithromycin is a potential, chemotherapeutic agent which possesses antimalarial activity and favourable pharmacokinetic properties. It is an azalide microbiocide derived semi-synthetically from macrolide erythromycin. Like other antibiotics, the azalide azithromycin has ability to inhibit protein synthesis on 70S ribosomes. SETTINGS: Experimental study. SUBJECTS AND METHODS: The parasiticidal profile was studied in five chloroquine sensitive and five chloroquine resistant P. falciparum isolates obtained from various places of India. The antimalarial activity was evaluated in P. falciparum schizont maturation by short term culture for 24 hours and by exposing the parasites to the drug for 96 hours. Parasites synchronized at ring stage were put for culture with various concentrations of azithromycin dihydrate (0.01-40[micro]/ml). RESULTS: At highest concentration (40[micro]/ml), parasite growth was inhibited totally in all 10 isolates. Antimalarial activity at 96 hours was greater than at 24 hours in both chloroquine sensitive and resistant parasites, which may indicate that the inhibition of parasite growth may occur at clinically achievable concentration of the drug when parasites were exposed for several asexual cycles. CONCLUSION: Azithromycin shows a potential for eventual use alone or in combination in the treatment of chloroquine sensitive and resistant P. falciparum malaria.

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Trends Parasitol 2002 Feb 1;18(2):75-80

Evolutionary studies of malaria vectors.

Donnelly MJ, Simard F, Lehmann T.

Division of Parasite and Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA., Liverpool, UK

The rationales given for studies of the population genetics of vectors are usually: (1) to predict the spread of genes, such as genes conferring insecticide resistance or possibly refractoriness to parasites and (2) to reveal novel insights into the epidemiology and transmission of vector-borne disease. The successful genetic transformation of mosquitoes has highlighted the need for a critical assessment of the rapidly accumulating body of data on the population genetics of malaria vectors. This article assesses how successful molecular genetic techniques have been in revealing new population patterns.

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Trends Parasitol 2002 Feb;18(2):49-50

Folic acid antagonism of sulfa drug treatments.

Bayly AM, Macreadie IG.

Commonwealth Scientific and Industrial Research Organisation (CSIRO), Health Sciences and Nutrition, 343 Royal Parade Parkville 3052 and Royal Melbourne Institute of Technology (RMIT) University, Bundoora, Victoria, Australia

Folic acid antagonizes the sulfa drug treatment of malaria. This antagonism has been mimicked in a yeast model system, where the growth inhibition by sulfa drugs can be confounded. In addition, yeast studies show that the inhibition is independent of folic acid utilization, suggesting that the antagonism occurs by an unexpected mechanism.

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Indian J Exp Biol 2001 Sep;39(9):902-5

Sustained release implants of chloroquine phosphate for possible use in chemoprophylaxis of malaria.

Saparia B, Solanki A, Murthy RSR.

Pharmacy department, Faculty of Technology and Engineering, MS University of Baroda, Vadodara, India.

Implants of chloroquine phosphate (CQP) using biodegradable polymer, gelatin (G) and cross-linked gelatin (CLG) were prepared and evaluated to assess their physicochemical properties and in vitro release profile. The mechanism and kinetics of release were studied to correlate the release phenomenon with the formulation parameters. Out of many batches of the implants investigated, the implant prepared with 20% gelatin at 2:1 drug polymer ratio, 10% crosslinking agent and 2% plasticizer (Batch J) was found to provide optimum release behavior conforming to the requirements of a long term implant for a week. In vivo studies conducted on albino rats showed consistent therapeutic blood level over a period of 7 days. Mean residence time (MRT) of the drug released in the body, calculated as the ratio of the area under the first moment curve (AUMC) to area under concentration time curve (AUC) was 72 hr for implant against 2.42 hr for subcutaneous injection.

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J Biol Chem 2002 Feb 4; [epub ahead of print]

Folding of the the plasmodium falicparum cysteine protease falcipain-2 is chaperone-like peptide and not the prodomain.

Sijwali PS, Shenai BR, Rosenthal PJ.

Medicine, University of California, San Francisco, San Francisco, CA 94143-0811.

Papain-family cysteine proteases of the malaria parasite Plasmodium falciparum, known as falcipains, are hemoglobinases and potential drug targets. Available data suggest that papain-family proteases require prodomains for correct folding into functional conformations. However, in prior studies of falcipain-2, an Escherichia coli expressed construct containing only a small portion of the prodomain refolded efficiently, suggesting that this enzyme differs in this regard from other papain-family enzymes. To better characterize the determinants of folding for falcipain-2, we expressed multiple pro- and mature constructs of the enzyme in E. coli and assessed their abilities to refold. Mature falcipain-2 refolded into active protease with very similar properties to those of proteins resulting from the refolding of proenzyme constructs. Deletion of a 17 amino acid amino-terminal segment of the mature protease yielded a construct incapable of correct folding, but inclusion of this segment in trans allowed folding to active falcipain-2. The prodomain was a potent, competitive, and reversible inhibitor of mature falcipain-2 (Ki 10-10 M). Our results identify a chaperone-like function of an amino-terminal segment of mature falcipain-2 and suggest that protease inhibition, but not the mediation of folding, is a principal function of the falcipain-2 prodomain.

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J Biol Chem 2002 Feb 4; 

Inhibition of Ca2+-calmodulin-dependent protein kinase blocks morphological differentiation of plasmodium gallinaceum Zygotes to Ookinetes.

Silva-Neto MA, Atella GC, Shahabuddin M.

Laboratory of Malaria and Vector Research, National Institutes of Health, Bethesda, MD 20892-0425.

Once ingested by mosquitoes, malaria parasites undergo complex cellular changes. These include zygote formation, transformation of zygote to ookinete, and differentiation from ookinete to oocyst. Within the oocyst, the parasite multiplies into numerous sporozoites. Modulators of intracellular calcium homeostasis A23187, MAPTAM, and TMB?8 blocked ookinete development, as did the calmodulin (CaM) antagonists W-7 and calmidazolium. Ca(2+)/CaM-dependent protein kinase (CaMK) inhibitor KN-93 also blocked zygote elongation, while its ineffective analog KN-92 did not have such effect. In vitro both zygote and ookinete extracts efficiently phosphorylated Autocamtide-2, a classic CaM kinase substrat which could be blocked by calmodulin antagonists W-7, calmidazolium and CaM kinase inhibitor K-93. These results demonstrated the presence of calmodulin dependent CaM kinase kinase activity in the parasite. KN-93-treated parasites, however, expressed the ookinete-specific enzyme chitinase and the ookinete surface antigen Pgs28 normally, suggesting that the morphologically untransformed parasites are biochemically mature ookinetes. In mosquitoes, KN-93-treated parasites did not develop as oocysts, while KN-92-treated parasites produced similar numbers of oocysts as controls. These data suggested that in Plasmodium gallinaceum morphological development of zygote to ookinete, but not its biochemical maturation, relies on CaMK activity and demonstrated that the morphological differentiation is essential for the further development of the parasite in infected blood fed mosquitoes.

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Trends Microbiol 2001 Feb;10(2):55-8

The role of antibodies to Plasmodium falciparum-infected-erythrocyte surface antigens in naturally acquired immunity to malaria.

Bull PC, Marsh K.

KEMRI Center for Geographic Medicine Research, Coast (CGMRC), PO Box 230, Kilifi, Kenya

Plasmodium falciparum, the most virulent species of human malaria parasite, causes 1-3 million deaths per year. Because this parasite is susceptible to naturally acquired host immunity the main burden of disease falls on young children. The mechanism of this immunity is still unclear. However, the parasite makes a considerable investment in the insertion of highly polymorphic antigens (parasite-infected-erythrocyte surface antigens, PIESA) on the infected erythrocyte surface, and these antigens are potentially important immune targets.

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Parasitol Res 2002 Jan;88(1):1-8

Molecular characterisation and chromosomal mapping of transcripts having tissue-specific expression in the malaria mosquito Anopheles gambiae: possible involvement in visual or olfactory processes.

Ricci I, Santolamazza F, Costantini C, Favia G.

Istituto di Parassitologia, Universita La Sapienza, Rome, Italy

We have compared the transcriptional activity of heads, antennae + palps, and carcasses in the mosquito Anopheles gambiae by means of differential display PCR (DD-PCR). Three transcripts specifically or preferentially expressed in the heads and in the antennae + palps have been selected. All are very similar to genes related to visual and olfactory mechanisms of several different organisms. They have been named Ag arrestin, Ag rLDL, and Ag dynamin. The potential of the DD-PCR technique in identifying genes involved in mosquito behaviour and the usefulness of the molecular characterisation of these transcripts are discussed.

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Nat Med 2002 Feb;8(2):166-70

IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages.

Carvalho LH, Sano Gi G, Hafalla JC, Morrot A, de Lafaille MA, Zavala F.

[1] Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York, USA [2] These authors contributed equally to this work.

CD4+ T cells are crucial to the development of CD8+ T cell responses against hepatocytes infected with malaria parasites. In the absence of CD4+ T cells, CD8+ T cells initiate a seemingly normal differentiation and proliferation during the first few days after immunization. However, this response fails to develop further and is reduced by more than 90%, compared to that observed in the presence of CD4+ T cells. We report here that interleukin-4 (IL-4) secreted by CD4+ T cells is essential to the full development of this CD8+ T cell response. This is the first demonstration that IL-4 is a mediator of CD4/CD8 cross-talk leading to the development of immunity against an infectious pathogen.

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Am J Epidemiol 2002 Feb 1;155(3):257-64

Rise in malaria incidence rates in South Africa: a small-area spatial analysis of variation in time trends.

Kleinschmidt I, Sharp B, Mueller I, Vounatsou P.

South African Medical Research Council, Durban, South Africa. Tropical Health Program, University of Queensland, Brisbane, Australia. Swiss Tropical Institute, Basel, Switzerland.

Using Bayesian statistical models, the authors investigated spatial and temporal variations in small-area malaria incidence rates for the period mid-1986 to mid-1999 for two districts in northern KwaZulu Natal, South Africa. Maps of spatially smoothed incidence rates at different time points and spatially smoothed time trends in incidence gave a visual impression of the highest increase in incidence occurring where incidence rates previously had been lowest. This was confirmed by conditional autoregressive models, which showed that there was a significant negative association between time trends and smoothed baseline incidence before the steady rise in caseloads began. Growth rates also appeared to be higher in the areas close to the Mozambican border. The main findings of this analysis were that: 1) the spatial distribution of the rise in malaria incidence is uneven and strongly suggests a geographic expansion of high-malaria-risk areas; 2) there is evidence of a stabilization of incidence in areas that had the highest rates before the current escalation of rates began; and 3) areas immediately adjoining the Mozambican border appear to have undergone larger increases in incidence, in contrast to the general pattern of low growth in the more northern, high-baseline-incidence areas, but this was not confirmed by modeling. Smoothing of small-area maps of incidence and growth in incidence (trend) is important for interpretation of the spatial distribution of disease incidence and the spatial distribution of rapid changes in disease incidence.

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J Chromatogr B Biomed Sci Appl 2002 Jan 5;766(1):3-12

Chromatographic characterization of synthetic peptides: SPf66 malaria vaccine.

Santovena A, Oliva A, Guzman F, Patarroyo ME, Llabres M, Farina JB.

Departamento de Ingenieria Quimica y Tecnologia Farmaceutica, Facultad de Farmacia, Universidad de La Laguna, Tenerife, Spain.

The development and validation of a quantitative size-exclusion chromatography (SEC) method for SPf66 malaria vaccine was achieved. The results show the reliability of the analytical method for the intended use. SPf66 malaria vaccine characterization was perforrmed using both relative techniques such as the conventional SEC and absolute techniques: mass spectrometry and multi-angle laser-light scattering detection. The relative and absolute molecular masses were in the 4600-18,000 Da range. The results clearly indicate the presence of the monomer and dimer species, whereas the third species could be the trimer or tetramer.

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Indian J Malariol 2000 Sep-Dec;37(3-4):88-96

Entomological and epidemiological studies on malaria in Rajmahal range, Bihar.

Das NG, Bhuyan M, Das SC.

Defence Research Laboratory, Post Bag No. 2, Tezpur-784 001, India.

The epidemiological investigations carried out in six tribal villages in Rajmahal range hill in south Bihar revealed average slide positivity rate (SPR) 25.1 ranging between 9.8 and 37.8 per cent. Plasmodium falciparum was the dominant parasite which accounted 64.2 per cent of the total infections. Results of mass blood survey indicated the presence of high percentage of asymptomatic carriers of malaria parasites in the local populace. In an entomological survey, 25 species of mosquitoes under five genera were collected in 20 trap nights. The average density of mosquitoes recorded was 230.6 per trap night. Anopheles mosquitoes alone accounted 72.8 per cent of the total collection whereas malaria vectors Anopheles maculatus, An. minimus, An. philippinensis, An. varuna and An. annularis accounted 32.8 per cent of the total anophelines collected. Both anopheline and culicine mosquitoes were found susceptible to DDT (4 per cent) and malathion (5 per cent) in 30 min exposure. Dissection of malaria vectors An. minimus, An. maculatus and An. philippinensis revealed very high percentage of parity rate (77.8 per cent) which gives a strong indication about their vectorial status in the transmission of malaria. Poor socio-economic condition, lack of sense of hygiene worsen the situation in the presence of asymptomatic carriers.

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Indian J Malariol 2000 Sep-Dec;37(3-4):82-7

Estimating parasite density in patients suffering from falciparum malaria in an endemic area in Kolkata.

Hati AK, Mondal B, Chaudhuri P, Purkayastha S, Mukherjee H, Mukhopadhyay AK.

Department of Medical Entomology, Calcutta School of Tropical Medicine, Kolkata-700 073, India.

Parasite density of one hundred patients suffering from falciparum malaria in an endemic area in Kolkata was determined using three different methods. In the first of these, parasite density per microlitre of blood in a patient was determined using parasite count adjusted by average WBC count (i.e. 8000/microliter) observed in microscopic fields of the thick film. In the remaining two methods, only raw (i.e. unadjusted) parasite counts in microscopic fields of the same slide were used. A statistical analysis was carried out in detail to compare these methods based on raw and adjusted parasite counts and also to find out a suitable method which can be used in practice. Estimating the density of parasites is of primary importance in determining the severity of infection. Furthermore, parasite density can help in identifying short-treatment and long-treatment failure vis-a-vis detection of development of resistance in P. falciparum against the drug used. This article reports some findings that indicate the existence of a potentially dangerous situation in the study area.

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Indian J Malariol 2000 Sep-Dec;37(3-4):74-81

Mosquito fauna and malaria vectors in Jairampur, district Changlang, Arunachal Pradesh.

Prakash A, Bhattacharyya DR, Mohapatra PK, Mahanta J.

Regional Medical Research Centre, N.E. Region (ICMR), Post Box No. 105, Dibrugarh-786 001, India.

In an entomological study, covering three biotopes like village, panikheti (wet rice cultivated land) and urban agglomeration, a total of 35 species of mosquitoes in eight genera were recorded in Jairampur area of Arunachal Pradesh. Two mosquito species–Orthopodomyia anopheloides and Tripteroides indicus were recorded for the first time in Arunachal Pradesh. Anopheles dirus and An. minimus, the two well-known malaria vectors were encountered in the study along with several potential vector species like An. annularis, An. culicifacies, An. maculatus group and An. philippinensis/nivipes. The diversity of mosquito species as well as the man-vector contact was maximum in the panikheti and minimum in the village biotope.

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Indian J Malariol 2000 Sep-Dec;37(3-4):68-73

Splenomegaly in school children in a remote tribal area of Dhole district, Maharashtra.

Ghosh K, Mukherjee MB, Surve RR, Shankarkumar U, Kate SL, Nagtilak SB, Colah RB, Tamankar AA, Mohanty D.

Institute of Immunohaematology (ICMR), 13th Floor, KEM Hospital Campus, Parel, Mumbai-400 012, India.

Sickle-cell gene is known to protect against P. falciparum infection and provides a selective survival advantage in those areas where P. falciparum infection is endemic. This protection is not absolute and many other factors, inherited and acquired also contribute to the immunity against P. falciparum infection. We investigated incidence of splenomegaly and typical history of malaria in the past two years in apparently healthy school children in a tribal area in Dhole district of Maharashtra to see whether the incidence of malaria (splenomegaly and typical history) was different in children having sickle-cell trait to that of those who did not have this trait. A total of 480 school children were clinically examined for splenomegaly and history of typical malaria fever and/or blood slide positivity for malaria in the past two years. About 9.55 per cent of normal population had either splenomegaly or convincing history of malarial infection in the past two years which is not statistically different from the sickle-cell trait patients having evidence of past malaria (8.79 per cent; p > 0.05).

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Indian J Malariol 2000 Sep-Dec;37(3-4):61-7

Prognostic implication of hypocalcemia and QTc interval in malaria.

Soni CL, Kumhar MR, Gupta BK, Singh VB, Srimali L, Nayak KC, Chadda VS.

Department of Medicine, S.P. Medical College, Bikaner-334 001, India.

Hundred confirmed cases of malaria were included in the present study to determine the clinical and prognostic implications of hypocalcemia and corrected QT interval (QTc) prolongation in malaria. Peripheral blood smear examination was done to determine the parasite species and the parasite load. Serum calcium level and QTc measurements in electrocardiogram were done for each patient. Fifty patients were of P. falciparum malaria (38 complicated and 12 uncomplicated), 40 of vivax malaria and 10 patients were having mixed (P. falciparum and P. vivax) infection. Hypocalcemia was found in 26 cases in which QTc was prolonged. Ten patients who had convulsions, all of them were having QTc prolongation and eight had hypocalcemia. A total number of eight patients had muscle spasm, of which six had QTc prolongation and four had hypocalcemia. There were 34 cases of cerebral malaria, of which 18 had hypocalcemia as well as QTc prolongation, 12 of them developed renal failure and 14 had high parasitaemia. Four patients died who had hypocalcemia and QTc prolongation due to hepatorenal syndrome. The mean parasite load, QTc interval and serum calcium were 2.69 +/- 1.0, 0.468 +/- 0.055 sec and 8.16 +/- 0.86 mg/dl respectively in complicated falciparum malaria; 1.6 +/- 0.55, 0.442 +/- 0.043 sec and 8.72 +/- 0.97 mg/dl in complicated mixed (Pf + Pv) infection. 1.33 +/- 0.52, 0.435 +/- 0.035 sec and 9.77 +/- 1.34 mg/dl in uncomplicated falciparum malaria and 1.35 +/- 0.58, 0.403 +/- 0.019 sec and 9.68 +/- 0.99 mg/dl in vivax malaria. The difference was significant between complicated falciparum and mixed (Pf + Pv) infection when compared to uncomplicated falciparum and vivax malaria (p < 0.05).

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Indian J Malariol 2000 Sep-Dec;37(3-4):53-60

Occupational malaria and health risk among select occupational health care employee groups in an urban hospital at Tirupati, A.P.

Rajasekhar M, Nandakumar NV.

Division of Environmental Biology, Department of Zoology, S.V. University, Tirupati-517 502, India.

Epidemiological studies on occupational environments are very meagre in the developing countries like India. For this reason an attempt was made in the present investigation to see the occupational risk of malaria among health care workers of Sri Venkateswara Ramnarayan Ruia Government General Hospital (SVRRGGH), Tirupati, Andhra Pradesh. The cohort studies revealed association between exposure to occupational (hospital) environment and malaria among hospital staff. Retrospective cohort studies were made. 1,454 subjects namely hospital staff exposed to occupational environment included civil assistant surgeons and physicians, the students of medicine, the students of nursing, permanent nursing staff and the class IV employees (class IV included janitorial, male nursing orderlies, female nursing orderlies, attenders, laundry workers and the rest). Retrospective epidemiological studies were carried out for four years on the cohorts and the hospital staff. The data showed statistically significant relative risk and attributable risk for malaria. Physicians and civil assistant surgeons showed no incidence of malaria. The relative risk for malaria in the class IV employees was 1.27, 0, 5.8 and 2.9 for the years 1995-98. The students of nursing showed 4.2, 2.42, 3.3 and 0 relative risk for malaria, whereas the students of medicine showed 2, 2, 2 and 1.6 for the years 1995 to 1998. The attributable risk was ranged from 21.76-82.70, 58.75-76.17, 50-80 for the class IV employees, the students of nursing and the students of medicine retrospectively. These results provide an evidence for an association between occupational environment and malaria for the hospital staff and is more prevalent among certain groups of the hospital staff.

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Indian J Malariol 2000 Mar-Jun;37(1-2):11-7

Malaria during pregnancy and its effects on foetus in a tribal area of Koraput District, Orissa.

Das LK.

Vector Control Research Centre (ICMR), Medical Complex, Indira Nagar, Pondicherry-605 006, India.

Malaria during pregnancy and its maternal and foetal complications was studied in Koraput district of Orissa–a tribal area, endemic for malaria. A total of 209 pregnant women with 738 pregnancy months were studied. The parasitic index among the pregnant women ranged between 10.8 and 25.6 per cent with peak incidence during post-monsoon months. There was a significant difference in parasite incidence between the primi- and multigravidae (p < 0.05) but difference was not observed between the trimesters. The mean haemoglobin (Hb) concentration declined to 8.4 g/dl (range 7.2-10.2 g/dl) at full-term and parturition from its initial level of 9.6 g/dl (range 7.2-12.8 g/dl). There was a significant difference (p < 0.05) in Hb concentration among the trimesters of pregnancy. There was no significant difference in the outcome of pregnancies in women with or without malaria prarasites in their peripheral blood. There was no significant difference in Hb concentrations between malaria parasite positive and negative pregnant women (p > 0.05). Significant difference was observed in the proportion of newborn positives from mothers with or without malaria parasites indicating a high degree of transplacental transmission. The overall foetal mortality rate was 21.5 per cent. The miscarriage, stillbirth, premature delivery leading to foetal and neonatal along with perinatal mortality constituted for 24.4, 13.3, 20 and 17.7 per cent of all mortalities respectively.

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Indian J Malariol 2000 Mar-Jun;37(1-2):1-10

Operational feasibility and efficacy of deltamethrin impregnated hessian curtains in comparison to HCH indoor residual spraying to control malaria in selected villages of District Ghaziabad (U.P.), India.

Ansari MA, Razdan RK.

Malaria Research Centre (ICMR), 20 Madhuvan, Delhi-110092, India.

A study was carried out in selected villages of District Ghaziabad to evaluate the operational feasibility and efficacy of hessian curtains impregnated with [email protected] mg/m2 in comparison to indoor residual spraying of [email protected] g/m2. The impregnation was carried out before onset of transmission and observations were continued up to two transmission periods. District Health Authorities have carried out HCH indoor residual spraying (IRS) as per schedule in the control village. Entomological evaluation revealed 87 per cent reduction of An. culicifacies up to six months in comparison to HCH indoor residual spraying. However, the reduction in densities of total mosquitoes was only 61.6 per cent. Follow-up studies revealed that the impact of deltamethrin impregnated curtains was diluted after 6-7 months. The results of bioassay tests revealed 100 per cent mortality up to 6-7 months. Epidemiological evaluation revealed 81.9 per cent reduction in total malaria cases as against 88.5 per cent with P. falciparum cases. Similar reduction was also observed when slide positivity rate (SPR), slide falciparum rate (SfR), cases/000 and Pf/000 were compared to corresponding village. Pilot studies are indicated to evaluate the relative efficacy of impregnated curtains, which is quite cheaper than conventional residual insecticide spraying (IRS).