EHP Library Malaria Bulletin 55: Mar 10-23, 2003

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Social Sciences and Malaria Control

Social science & medicine : (1982), 2002, 55 (12) 2215-2226

Strategies to improve adherence to recommended chloroquine treatment regimes: a quasi-experiment in the context of integrated primary health care delivery in Ghana

IRENE AKUA AGYEPONG; ANSAH Evelyn; GYAPONG Margaret; ADJEI Sam; BARNISH Guy; EVANS David

District Health Administration, P.O. Box 1, Dodowa, Ghana; Health Research Unit, P.O. Box 184, Adabraka, Ghana; Ghana Health Service, P.O. Box M44, Accra, Ghana; Liverpool School of Topicial Medicine, Liverpool L3 5QA, United Kingdom; World Health Organization, 1211 Geneva, Switzerland.

This paper presents the results of an intervention study carried out as part of the activities of a District Health Management Team responsible for integrated primary health care delivery in a rural district in Ghana. The aim was to test the impact of a combination of improved information provision to patients and drug labeling on adherence to recommended anti-malarial treatment regimens focusing on oral chloroquine, for the outpatient management of acute uncomplicated malaria. The study had a quasi-experimental pre-test post-test control group design with partly random allocation by clinic. The results show that the intervention resulted in an improved flow of information to clients prescribed chloroquine, and better labeling of drugs for the home treatment of acute clinical episodes of malaria in the intervention area. Improvements in adherence occurred in all clinics. However, improvements in adherence were most marked in the clinic that was worst performing at the start of the intervention. Implications of the results for improving adherence to chloroquine therapy on an outpatient basis are discussed. Soc Sci Med 2003 Apr;56(8):1705-17

Social and health determinants of the efficiency of cotton farmers in Northern Cote d’Ivoire. Audibert M, Mathonnat J, Henry MC. Centre d’Etudes et de Recherches sur le Developpement International, Universite d’Auvergne, 65 Bd. F. Mitterrand, 63000, Clermont-Ferrand, France.

This article assesses the role of malaria and some social determinants on the agricultural development and more precisely on efficiency in the context of cotton crop in the Korhogo region in the North of Cote d’Ivoire. Data envelopment analyses (DEA) was first applied for the purpose of calculating relative efficiencies in production. A Tobit regression model was then used to explain the variation in the DEA scores and check the hypotheses that the efficiency deviations between farmers can be explained by the disparity of malaria morbidity rate among the farmers and their family, by social cohesiveness and cultural behaviour.Field data were collected by the authors between March 1997 and February 1998 on 700 rural households living in three rice production systems differently exposed to the malaria risk. Two malaria indicators were used for the active (11-55 years old) family members of the farm: Plasmodium falciparum infection rate and high parasite density infection rate. The DEA model was applied on the sub-sample of cotton growers (about one third of the households of the full sample). Results of the different DEA and Tobit models (depending of the production process hypothesis) show that high parasite density infection has a direct and indirect negative effect on efficiency in the cotton crop. They also show that more cotton growers in the village improve efficiency, although villages where cotton is growing more widespread have weaker social cohesion. PMID: 12639587 PubMed J Ethnopharmacol 2003 Feb;84(2-3):235-239

In vitro antiplasmodial activity of some plants used in Kisii, Kenya against malaria and their chloroquine potentiation effects. Muregi FW, Chhabra SC, Njagi EN, Lang’at-Thoruwa CC, Njue WM, Orago AS, Omar SA, Ndiege IO. Biochemistry Department, Kenyatta University, P.O. Box 43844, Nairobi, Kenya.

Fifty-five organic and aqueous extracts of 11 plants used in malaria therapy in Kisii District, Kenya were tested in vitro against chloroquine (CQ)-sensitive and resistant strains of Plasmodium falciparum. Of the plants tested, 73% were active (IC(50)<100 &mgr;g/ml). Three plants, Vernonia lasiopus, Rhamnus prinoides and Ficus sur afforded extracts with IC(50) values ranging less than 30 &mgr;g/ml against both CQ-sensitive and resistant strains. Combination of some extracts with CQ against the multi-drug resistant P. falciparum isolate V1/S revealed some synergistic effect. The plant extracts with low IC(50) values may be used as sources for novel antimalarial compounds to be used alone or in combination with CQ. PMID: 12648820 [PubMed – as supplied by publisher] Trends Parasitol 2003 Mar;19(3):144-9

Human migration, mosquitoes and the evolution of Plasmodium falciparum. Hume JC, Lyons EJ, Day KP. Peter Medawar Building for Pathogen Research, Dept of Zoology, University of Oxford, OX1 3SY, Oxford, UK.

To date, coalescent analysis of the Plasmodium falciparum genome sequence has failed to provide a unifying theory regarding the parasite’s evolution. While a better understanding of the evolution of the malaria genome will undoubtedly clarify the current controversy, the importance of the parasite’s interplay with both the human host and mosquito vector cannot be underestimated. Changes in the population biology or ecology of either one of these species have consequences for malaria transmission and this was never more apparent than in the environmental changes brought about by the advent of agriculture. PMID: 12643998 Trends Parasitol 2003 Mar;19(3):135-43

The Plasmodium sporozoite journey: a rite of passage. Kappe SH, Kaiser K, Matuschewski K. Michael Heidelberger Division, Dept of Pathology, New York University School of Medicine, 10016, New York, NY, USA.

Sporozoites are the most versatile of the invasive stages of the Plasmodium life cycle. During their passage within the mosquito vector and the vertebrate host, sporozoites display diverse behaviors, including gliding locomotion and invasion of, migration through and egress from target cells. At the end of the journey, sporozoites invade hepatocytes and transform into exoerythrocytic stages, marking the transition from the pre-erythrocytic to the erythrocytic part of the life cycle. This article discusses recent work, mostly done with rodent malaria parasites, that has contributed to a better understanding of the sporozoites’ complex biology and which has opened up new avenues for future sporozoite research. PMID: 12643997 [PubMed – in process] Trends Parasitol 2003 Mar;19(3):115-20

Can primaquine therapy for vivax malaria be improved? Baird JK, Rieckmann KH. US Naval Medical Research Unit #2, American Embassy Jakarta, Fleet Post Office, Asia-Pacific 96520-8132, USA.

The incidence and range of endemic malaria caused by Plasmodium vivax has expanded during the past 30 years. This parasite forms hypnozoites in the liver, creating a persistent reservoir of infection. Primaquine (PQ), introduced 50 years ago, is the only drug available to eliminate hypnozoites. However, lengthy treatment courses and follow-up periods are not conducive to assessing the effectiveness of this drug in preventing relapses. Resistance to standard therapy could be widespread. Studies are urgently needed to gauge this problem and to determine the safety, tolerability and efficacy of shorter courses and higher doses of PQ. PMID: 12643993 [PubMed – in process] Trends Parasitol 2003 Mar;19(3):103-5

The mosquito genome: perspectives and possibilities. Land KM. Sandler Center for Basic Research in Parasitic Diseases, University of California, 94143, San Francisco, CA, USA.

Anopheles gambiae is the mosquito vector responsible for transmitting Plasmodium falciparum, a malaria parasite of humans. With the emergence of genome projects for a variety of prokaryotic and eukaryotic microorganisms, there has been a long-standing interest in sequencing the genomes of the malaria parasite and its insect vector. This tour de force effort has now been completed and reported. The alignment of putative orthologs in An. gambiae with those of Drosophila melanogaster highlights several similarities and differences. These findings could have implications in: (1) identifying new targets for insecticide development; (2) strengthening our understanding of the developmental biology of mosquitoes; and (3) possibly controlling pathogen transmission. A brief overview of these interesting findings and the implications for further studies will be discussed here. PMID: 12643988 [PubMed – in process] J Infect 2003 Apr;46(3):164-72

Does Infection with Human Immunodeficiency Virus Affect the Antibody Responses to Plasmodium falciparum Antigenic Determinants in Asymptomatic Pregnant Women? Ayisi JG, Branch OH, Rafi-Janajreh A, van Eijk AM, ter Kuile FO, Rosen DH, Kager PA, Lanar DE, Barbosa A, Kaslow D, Nahlen BL, Lal AA. Centre for Vector Biology & Control Research, Kenya Medical Research Institute, Kisumu, Kenya.

OBJECTIVES: HIV-seropositive pregnant women are more susceptible to malaria than HIV-seronegative women. We assessed whether HIV infection alters maternal and cord plasma malarial antibody responses and the mother-to-infant transfer of malaria antibodies.METHODS: We determined plasma levels of maternal and cord antibodies [Immunoglobulin (IgG)] to recombinant malarial proteins [merozoite surface protein 1 (MSP-1(19kD)), the erythrocyte binding antigen (EBA-175)], the synthetic peptides [MSP-2, MSP-3, rhoptry associated protein 1 (RAP-1), and the pre-erythrocytic stage, circumsporozoite protein (NANP)(5)] antigenic determinants of Plasmodium falciparum; and tetanus toxoid (TT) by ELISA among samples of 99 HIV-seropositive mothers, 69 of their infants, 102 HIV-seronegative mothers and 62 of their infants.

RESULTS: The prevalence of maternal antibodies to the malarial antigenic determinants ranged from 18% on MSP3 to 91% on EBA-175; in cord plasma it ranged from 13% to 91%, respectively. More than 97% of maternal and cord samples had antibodies to TT. In multivariate analysis, HIV infection was only associated with reduced antibodies to (NANP)(5) in maternal (P=0.001) and cord plasma (P=0.001); and reduced mother-to-infant antibody transfer to (NANP)(5) (P=0.012). This effect of HIV was independent of maternal age, gravidity and placental malaria. No consistent HIV-associated differences were observed for other antigenic determinants.

CONCLUSION: An effect of HIV infection was only observed on one malarial antigenic determinant, suggesting that the increased susceptibility to malaria among HIV-infected pregnant women may not be explained on the basis of their reduced antibody response to malaria antigens. PMID: 12643865 [PubMed – in process] Malar J 2003 Feb 19;2(1):3

Epidemiological models for the spread of anti-malarial resistance. Koella J, Antia R. Laboratoire de Parasitologie Evolutive, Universite P, & M, Curie, CNRS UMR 7103, 7 quai St, Bernard CC237, 75252 Paris, France. Email: [email protected]

BACKGROUND: The spread of drug resistance is making malaria control increasingly difficult. Mathematical models for the transmission dynamics of drug sensitive and resistant strains can be a useful tool to help to understand the factors that influence the spread of drug resistance, and they can therefore help in the design of rational strategies for the control of drug resistance. METHODS: We present an epidemiological framework to investigate the spread of anti-malarial resistance. Several mathematical models, based on the familiar Macdonald-Ross model of malaria transmission, enable us to examine the processes and parameters that are critical in determining the spread of resistance. RESULTS: In our simplest model, resistance does not spread if the fraction of infected individuals treated is less than a threshold value; if drug treatment exceeds this threshold, resistance will eventually become fixed in the population. The threshold value is determined only by the rates of infection and the infectious periods of resistant and sensitive parasites in untreated and treated hosts, whereas the intensity of transmission has no influence on the threshold value. In more complex models, where hosts can be infected by multiple parasite strains or where treatment varies spatially, resistance is generally not fixed, but rather some level of sensitivity is often maintained in the population. CONCLUSIONS: The models developed in this paper are a first step in understanding the epidemiology of anti-malarial resistance and evaluating strategies to reduce the spread of resistance. However, specific recommendations for the management of resistance need to wait until we have more data on the critical parameters underlying the spread of resistance: drug use, spatial variability of treatment and parasite migration among areas, and perhaps most importantly, cost of resistance. PMID: 12643812 Arch Inst Pasteur Madagascar 2002;68(1-2):79-85

Malaria in Madagascar [Article in French] Raharimalala LA, Rabarijaona L, Randrianarivelojosia M, Razanavololo F, Rason MA, Andrianantenaina HB, Andrianaivolambo L, Rakotoniaina JC, Leong Pock Tsi JM, Rajaonarivelo E, Leon T, Duchemin JB, Ariey F. Institut Pasteur de Madagascar, Groupe de Recherche sur le Paludisme, BP 1274-101 Antananarivo-Madagascar.

Madagascar is a tropical island affected by many natural disasters. The eastern coastal zone–an area of perennial malaria transmission–is regularly exposed to cyclones. Few malaria studies have been done in this area of Madagascar, and none have examined the potential relationship between malaria and natural disasters. A mobile team spent six weeks in the fields doing three lines of research: an entomological study by catching mosquitoes and determining their species: a therapeutic study of chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) according to a 14 days WHO protocol and also a study of physician’s diagnostic ability. Physicians were asked to make a presumptive clinical diagnosis of all febrile patients, and these results were compared to those obtained from blood smear examinations. The entomological study found three major vectors species: Anopheles gambiae, An. funestus and An. mascarensis. The therapeutic study showed that SP was 100% effective (n = 13) and only one case of CQ treatment failure was recorded (1/15). Finally the diagnostic study demonstrated that presumptive diagnosis of malaria based on the only clinical signs leads to an over-estimation of malaria frequency. Over 68% (102/149) of febrile patients were diagnosed by physicians to have malaria while only 52 (34.9%) were proven positive. Of the 47 patients diagnosed clinically as malaria-negative, 12 (25.5%) turned out to be positive. Outbreaks of malaria during or after natural disasters in Madagascar can be successfully treated with either CQ or SP, but compliance may be better with SP since it requires only one dose. Perhaps equally important in the context of natural disasters is to have the capacity to make a definitive diagnosis, and the dipsticks should be made available. PMID: 12643099 [PubMed – in process] Arch Inst Pasteur Madagascar 2002;68(1-2):73-8

Malaria policy in Madagascar [Article in French] Randrianarivelojosia M, Rakotonjanabelo LA, Mauclere P, Ratsimbasoa A, Raharimalala LA, Ariey F. Institut Pasteur de Madagascar, Groupe de Recherche sur le Paludisme, BP 1274-101 Antananarivo-Madagascar.

To redefine strategy and policy to cure or to prevent malaria, there is a need to get relevant and updated data on Plasmodium sp sensitivity level to antimalarial drugs. Thus, in September 1999, the Madagascan Ministry of Health and the Institut Pasteur de Madagascar (IPM) formed a network named RER for malaria resistance surveillance. To alleviate the lack of experienced medical teams within the health centres, and due to technical and logistic matters, as part of the network activities, it was decided to give a start with the in vitro studies which are carried out at IPM. In vitro sensitivity testing is done by use of the isotopic method. Results from the study done in 2001 demonstrate that the Madagascan P. falciparum isolates are susceptible to amodiaquine (n = 215), to cycloguanil (n = 56), to pyrimethamine (n = 98) and to quinine (n = 214). One isolate (1/110 i.e. 0.9%) of mefloquine-resistant phenotype is detected from the Eastern region. P. falciparum susceptibility to chloroquine is satisfactory with 95.4% (206/216) of in vitro sensitive isolates. RER arises from the partnership and collaboration between the Madagascan Ministry of Health and the IPM. The network set-up is presented. The usefulness of the in vivo approach, and the in vitro investigations (chemosusceptibility test and screening of mutations accounting for resistance to chloroquine) to monitor the emergence and the dissemination of drug-resistant parasites in Madagascar as well as in the subregion of the Indian Ocean is discussed. PMID: 12643098 Drug Chem Toxicol 2003 Feb;26(1):59-71

Influence of chloroquine treatment and Plasmodium falciparum malaria infection on some enzymatic and non-enzymatic antioxidant defense indices in humans. Farombi EO, Shyntum YY, Emerole GO. Department of Biochemistry, Drug Metabolism and Toxicology, Research Laboratories, College of Medicine, University of Ibadan, Nigeria. Email: [email protected]

BACKGROUND: It is known that malaria infection is accompanied by increased production of reactive oxygen species (ROS) and that malaria parasites are sensitive to oxidative damage. This has been proved by the efficacy of some antimalarial drugs that are known to act via generation of ROS when administered clinically or experimentally.

OBJECTIVE: There is lack of information on the effect of chloroquine on the antioxidant defense systems of normal and malaria infected humans. Since chloroquine has remained the mainstay of therapeutic regimen in malaria endemic zones, the present investigation was therefore undertaken to study the status of blood antioxidant defense mechanism, and oxidative stress following chloroquine treatment in normal and plasmodium infected humans.

METHODS: Ten healthy persons (5 males and 5 females) with the same age range (18-35 years) were taken as control group. Ten other individuals were treated with 25 mg/kg body with chloroquine over three days. Ten patients with malaria, not under antimalarial therapy were taken as another group, while another set of 10 patients with malaria were treated with 25 mg/kg body weight over three days. RESULTS: The activity of superoxide dismutase was increased by 23% in individuals treated with chloroquine compared to controls while the activity of the enzyme decreased by 26% in malaria patients and by 43% in malaria patients treated with chloroquine. In all the treatment groups, the activities of catalase and glutathione peroxidase were lowered (P < 0.001). Similarly the levels of vitamins A, C, and beta-carotene were decreased in the treatment groups while plasma ceruloplasmin was increased in the groups. Glutathione and cholesterol levels were decreased while malondialdehyde level was increased significantly.

CONCLUSION: Chloroquine treatment mediated oxidative stress in the host and this effect was exacerbated in Plasmodium falciparum infected patients administered with the drug. PMID: 12643041 Proc R Soc Lond B Biol Sci 2003 Mar 7;270(1514):545-54

The de novo selection of drug-resistant malaria parasites. White NJ, Pongtavornpinyo W. Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand; and Centre for Tropical Diseases, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, OX3 9DU, UK.

Antimalarial drug resistance emerges de novo predominantly in areas of low malaria transmission. Because of the logarithmic distribution of parasite numbers in human malaria infections, inadequately treated high biomass infections are a major source of de novo antimalarial resistance, whereas use of antimalarial prophylaxis provides a low resistance selection risk. Slowly eliminated antimalarials encourage resistance largely by providing a selective filter for resistant parasites acquired from others, and not by selecting resistance de novo. The de novo emergence of resistance can be prevented by use of antimalarial combinations. Artemisinin derivative combinations are particularly effective. Ensuring adequate treatment of the relatively few heavily infected patients would slow the emergence of resistance. PMID: 12641911 Am J Trop Med Hyg 2003 Feb;68(2):186-90

Human genetic polymorphisms and asymptomatic Plasmodium falciparum malaria in Gabonese schoolchildren. Mombo LE, Ntoumi F, Bisseye C, Ossari S, Lu CY, Nagel RL, Krishnamoorthy R. Centre International de Recherches Medicales de Franceville, Franceville, Gabon. Email: [email protected]

Several studies have focused their attention on the relationship between host genetic factors and susceptibility/resistance to severe malaria. However, there is a paucity of information concerning the role of host genetic factors in asymptomatic malaria, a form of low-grade Plasmodium falciparum infection without clinical symptoms. We investigated in this study the potential relationship between the host (human) genetic polymorphisms (glucose-6-phosphate dehydrogenase [G6PD], mannose binding lectin [MBL], tumor necrosis factor alpha TNFalpha and (-238), and nitric oxide synthase 2 NOS2) and the prevalence and profile of asymptomatic P. falciparum infection in 158 Gabonese schoolchildren. We found that G6PD A- heterozygous females (18 of 74) have a low prevalence of asymptomatic malaria (38.9% versus 67.3%; P = 0.03, by chi-square test). Children heterozygous for TNFalpha(-238) (25 of 156) carry high number of diverse infecting parasite genotypes (2.5 versus 1.99; variance F = 3.05). No statistically significant association was found between MBL, TNFalpha(-308), or NOS2 polymorphisms and asymptomatic malaria. Upon combining our data on asymptomatic forms with those from the literature for others forms, we conclude that G6PD A- heterozygous females are protected against all forms of P. falciparum malaria, and that the TNFalpha(-238A) allele confers protection against clinical malaria. PMID: 12641410 Am J Trop Med Hyg 2003 Feb;68(2):182-5

Normal riboflavin status in malaria patients in Gabon. Traunmuller F, Ramharter M, Lagler H, Thalhammer F, Kremsner PG, Graninger W, Winkler S. Department of Internal Medicine I, Division of Infectious Diseases, University of Vienna, Vienna, Austria. Email: [email protected]

Previous publications reported commonly the occurrence of riboflavin deficiency and a positive correlation between riboflavin status and parasitemia in patients with Plasmodium falciparum malaria. In these studies, riboflavin status was determined by erythrocyte glutathione reductase activation coefficients (EGRACs). Inherited low erythrocyte glutathione reductase activity is highly prevalent in malarial regions, however. To rule out falsely diagnosed riboflavin deficiency in affected patients, we conducted an investigation using a high-performance liquid chromatography method (HPLC) instead of the EGRAC method. In 29 infants (age range, 1-5 years), 22 schoolchildren (age range, 6-12 years), and 33 adolescents and adults (age range, 13-74 years) from Lambarene, Gabon, with acute P. falciparum malaria, plasma concentrations of riboflavin, flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD) were measured by HPLC. Results were correlated with parasite densities. Profiles of plasma concentrations of all 3 flavin compounds were within the normal range in all patients. Concentrations of free riboflavin were not different between the 3 age groups. In adolescents and adults, FMN and FAD concentrations were higher than in infants (P = 0.002 and P = 0.001) and schoolchildren (P = 0.003 and P = 0.002). Comparing children with hyperparasitemic and uncomplicated malaria, no difference in the concentrations of either flavin compound was found. Neither the concentrations of free riboflavin nor the concentrations of one of the flavin nucleotides correlated with parasitemia within subgroups of age or of children with uncomplicated and hyperparasitemic malaria. Our data indicate that nutritional riboflavin deficiency might have been overestimated in previous malaria studies and do not support a relationship between flavin concentrations and parasitemia in P. falciparum malaria. PMID: 12641409 Am J Trop Med Hyg 2003 Feb;68(2):177-81

Strong association between house characteristics and malaria vectors in Sri Lanka. Konradsen F, Amerasinghe P, van der Hoek W, Amerasinghe F, Perera D, Piyaratne M. Department of International Health, University of Copenhagen, Copenhagen, Denmark.

The objective of this study was to determine whether house characteristics could be used to further refine the residual insecticide-spraying program in Sri Lanka. Indoor-resting mosquito densities were estimated in 473 houses based on fortnightly collections over a two-and-a-half-year period. The type of house construction and the exact location of all houses were determined. In a multivariate analysis, distance of less than 750 meters between a house and the main vector-breeding site was strongly associated with the presence of Anopheles culicifacies in the house (odds ratio [OR] 4.8, 95% confidence interval [CI] 3.4-6.8) and to a lesser extent with the presence of An. subpictus (OR 1.4, 95% CI 1.1-1.7). Poor housing construction also was an independent risk factor (OR for An. culicifacies 1.3, 95% CI 1.0-1.9; OR for An. subpictus 1.3, 95% CI 1.0-1.6). It is recommended that a malaria control strategy focus on residential areas within 750 meters of streams and rivers, with special attention given to areas with the poorest type of house construction. PMID: 12641408 Am J Trop Med Hyg 2003 Feb;68(2):169-76

Malaria transmission in urban sub-Saharan Africa. Robert V, Macintyre K, Keating J, Trape JF, Duchemin JB, Warren M, Beier JC. Institut de Recherche pour le Developpement, France. Email: [email protected]

The rapid increase in the world’s urban population has major implications for the epidemiology of malaria. A review of malaria transmission in sub-Saharan African cities shows the strong likelihood of transmission occurring within these sprawling cities, whatever the size or characteristics of their bioecologic environment. A meta-analysis of results from studies of malaria transmission in sub-Saharan Africa shows a loose linear negative relationship between mean annual entomologic inoculation rates (EIR) and the level of urbanicity. Few studies have failed to find entomologic evidence of some transmission. Our results show mean annual EIRs of 7.1 in the city centers, 45.8 in periurban areas, and 167.7 in rural areas. The impact of urbanization in reducing transmission is more marked in areas where the mean rainfall is low and seasonal. Considerable variation in the level of transmission exists among cities and within different districts in the same city. This article presents evidence from past literature to build a conceptual framework to begin to explain this heterogeneity. The potential for malaria epidemics owing to decreasing levels of natural immunity may be offset by negative impacts of urbanization on the larval ecology of anopheline mosquitoes. Malaria control in urban environments may be simpler as a result of urbanization; however, much of what we know about malaria transmission in rural environments might not hold in the urban context. PMID: 12641407 Am J Trop Med Hyg 2003 Feb;68(2):161-8

Transmission of mixed Plasmodium species and Plasmodium falciparum genotypes. Arez AP, Pinto J, Palsson K, Snounou G, Jaenson TG, do Rosario VE. Centro de Malaria e outras Doencas Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal. Email: [email protected]

We studied malaria transmission by comparing parasite populations in humans and mosquito vectors at the household level. Blood samples were collected from all inhabitants for microscopic detection of gametocytes and polymerase chain reaction analysis. The next morning, blood-fed resting mosquitoes were collected inside the bed nets used by the individuals surveyed the previous afternoon. After 8 days of maintenance, mosquitoes were dissected, and midguts and salivary glands were recovered for polymerase chain reaction analysis. Results showed that parasite distribution was the same in the 2 hosts when compared at each household but was different when whole populations were analyzed. Different associations of Plasmodium species seem to occur in humans (Plasmodium falciparum/Plasmodium malariae) and mosquitoes (P. falciparum/Plasmodium ovale). Regarding P. falciparum infections, a higher proportion of single-genotype infections and less allele diversity are observed in mosquitoes than in humans. PMID: 12641406 Am J Trop Med Hyg 2003 Feb;68(2):159-60

Case report: An unusual late relapse of Plasmodium vivax malaria. Mangoni ED, Severini C, Menegon M, Romi R, Ruggiero G, Majori G. Dipartimento di Medicina Interna, Seconda Universita di Napoli, Ospedale Gesu e Maria, Naples, Italy.

We observed an unusual case of Plasmodium vivax malaria who presented with an initial relapse four years after the primary infection. This occurred in Cameroon, where the patient, a 56-year-old priest, acquired a mild form of malaria and was treated with only chloroquine. Since he returned to Italy, he had not experienced any malaria-like symptoms, had not visited any other areas endemic for malaria, and had not received a blood transfusion. Blood smear microscopy confirmed the presence of Plasmodium spp. parasites, but unclear morphologic characteristics did not allow discrimination between P. vivax and P. ovale. A nested polymerase chain reaction-based molecular analysis identified P. vivax as the plasmodial species responsible. This case emphasizes the importance of taking into account the possibility of a very late initial relapse of P. vivax malaria and the relevant issues in terms of infection control. PMID: 12641405 Am J Trop Med Hyg 2003 Feb;68(2):153-8

Descriptive study on the efficacy and safety of artesunate suppository in combination with other antimalarials in the treatment of severe malaria in Sudan. Awad MI, Alkadru AM, Behrens RH, Baraka OZ, Eltayeb IB. Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan.

Documentation on the efficacy of artesunate in Africa is limited, and no experience of artesunate use in Sudan is documented. Severe malaria in rural areas of Sudan, where facilities for the safe and effective use of parenteral quinine are lacking, is a frequent problem. Early treatment with artesunate suppositories would provide a simple method for use by unskilled staff and would be an alternative approach to treat malaria in settings with poor resources. We describe a hospital-based study of rectal artesunate in 100 adult patients with severe falciparum malaria with a dose derived from pharmacokinetic data (200 mg every 8 hours) over 3 days, which halted progression of severe disease and had a low fatality rate. The dosage schedule led to a rapid clinical response and reduced parasite clearance and fever subsidence times of (31.5 +/- 10.1 hours) and (31.4 +/- 11.1 hours). The sequential treatment of rectal artesunate with either doxycycline or pyrimethamine/sulfadoxine or mefloquine resulted in similar clinical cure rates of around 100%, and the combination of artesunate with either doxycycline or pyrimethamine/sulfadoxine was equally effective as mefloquine in preventing recrudescence. There were no significant adverse effects or signs of toxicity related to the treatment observed during the 28-day follow-up. The combination regimens could be used in areas where there is limited access to parenteral therapy for malaria. PMID: 12641404 Am J Trop Med Hyg 2003 Feb;68(2):147-52

Recrudescence in artesunate-treated patients with falciparum malaria is dependent on parasite burden not on parasite factors. Ittarat W, Pickard AL, Rattanasinganchan P, Wilairatana P, Looareesuwan S, Emery K, Low J, Udomsangpetch R, Meshnick SR. Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.

Artemisinin derivatives are first-line antimalarial drugs in Thailand. No firm evidence of clinically relevant artemisinin resistance exists. When used as monotherapy, artesunate has been associated with a high treatment failure (recrudescence) rate, which could be due to low-level artemisinin resistance. To understand the causes of recrudescence, we retrospectively studied a cohort of 104 malaria patients treated with artesunate monotherapy, 32 of whom recrudesced. There was no difference in in vitro artesunate sensitivities between 6 nonrecrudescent isolates and 16 paired admission and recrudescent isolates. Paired admission and recrudescent isolates from 10 patients were genotyped; only 3 had pfmdr1 mutations. Patients with admission parasitemias >10,000 per microl had a 9-fold higher likelihood of recrudescence (adjusted odds ratio) compared with patients with lower parasitemias. This study suggests (1) recrudescence after treatment with artesunate is not the result of inherent parasite resistance, and (2) admission parasitemia may be useful in choosing therapeutic options. PMID: 12641403 Am J Trop Med Hyg 2003 Feb;68(2):140-2

Drug-resistant malaria in Bangladesh: an in vitro assessment. Noedl H, Faiz MA, Yunus EB, Rahman MR, Hossain MA, Samad R, Miller RS, Pang LW, Wongsrichanalai C. U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

Forty-four Plasmodium falciparum isolates from Bangladesh and 22 from western Thailand were successfully tested for their drug susceptibility. High degrees of resistance were observed against chloroquine with geometric mean IC50s of 114.25 and 120.5 nM, respectively, for Bangladesh and western Thailand. Most isolates from both sites were sensitive to quinine, and all were sensitive to artesunate. Many isolates were considered in vitro resistant to mefloquine, but the geometric mean IC50 for the Thai isolates (98.79 nM) was 1.6 times (P = 0.002) higher than that of isolates from Bangladesh (60.3 nM). The high prevalence of in vitro mefloquine resistance in Bangladesh suggests that close surveillance is necessary to delay widespread multidrug resistant problems in the area. Am J Trop Med Hyg 2003 Feb;68(2):127-32 Comparative efficacy of aminoquinoline-antifolate combinations for the treatment of uncomplicated falciparum malaria in Kampala, Uganda. Gasasira AF, Dorsey G, Nzarubara B, Staedke SG, Nassali A, Rosenthal PJ, Kamya MR. Makerere University Medical School, Kampala, Uganda. Resistance to chloroquine (CQ) requires its replacement as first-line therapy for uncomplicated malaria in much of Africa. Combination therapy may improve efficacy and delay the selection of resistant malaria parasites. Combinations of sulfadoxine-pyrimethamine (SP) with 4-aminoquinolines offer affordable and available alternatives to CQ. We conducted a randomized, single-blinded trial to compare the efficacy of SP monotherapy with combinations of SP and either CQ or amodiaquine (AQ) for the treatment of uncomplicated falciparum malaria in patients over 6 months of age in Kampala, Uganda. Of the 448 patients enrolled, 428 (95%) completed follow-up. Clinical treatment failure after 14 days occurred in 21/140 (15.0%, 95% CI 9.5-22.0%) SP-treated, 11/152 (7.2%, 95% CI 3.7-12.6%) SP/CQ-treated, and 0/136 (0%, 95% CI 0-2.7%) SP/AQ-treated patients. Combination therapies were safe and offered superior efficacy to SP monotherapy. SP/AQ was the most efficacious. This low-cost combination regimen may provide an optimal alternative to CQ for the treatment of uncomplicated malaria in Uganda. PMID: 12641399 Vaccine 2003 Apr 2;21(15):1650-7

Expression of malaria transmission-blocking vaccine antigen Pfs25 in Pichia pastoris for use in human clinical trials. Zou L, Miles AP, Wang J, Stowers AW. Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 20852, Rockville, MD, USA.

In previously published studies, Saccharomyces cerevisiae recombinant protein expression systems have been employed to express the malaria parasite antigen Pfs25, a candidate transmission-blocking vaccine antigen against Plasmodium falciparum malaria. However, despite having been in two Phase 1 trials, the recombinant Pfs25 so produced (previously called TBV25H) exists as a mixture of two monomeric protein conformational forms, Pfs25H-A and Pfs25H-B. In this study, we optimized the expression and purification of the two Pfs25H conformers in S. cerevisiae, and characterized their biochemical and antigenic properties, immunogenicities, and transmission-blocking activities. Pfs25H-A is apparently homogeneous, and has the correct conformation as measured by monoclonal antibody recognition. It is, however, expressed at a low yield of only 0.19mg/l. By contrast, Pfs25H-B is produced as a heterogeneous population of molecules that do not seem to have the correct conformation. Nonetheless, both forms appear equally effective in their ability to produce transmission-blocking antibodies in mice. To address the low yield seen with S. cerevisiae, we also expressed Pfs25 in Pichia pastoris. P. pastoris is apparently superior to S. cerevisiae in producing higher yield, immunologically more potent, biologically more active Pfs25H-A. East Afr Med J 2002 Jul;79(7):343-6

Prophylactic effect of multi-herbal extract ‘Agbo-Iba’ on malaria induced in mice. Nwabuisi C. Department of Medical Microbiology and Parasitology, Faculty of Health Sciences, University of Ilorin, P.M.B. 1515, Ilorin, Nigeria.

OBJECTIVE: To determine the efficacy of a multi-herbal preparation extract of ‘Agbo-Iba’ on rodent malaria induced in mice. DESIGN: An experimental design in which mice were divided into four groups A,B,C,D representing control, prophylactic, chloroquine and ‘Agbo-Iba’ groups respectively. Each mouse was intraperitoneally inoculated with Plasmodium yoelii nigeriensis and treated with oral herbal extract or chloroquine syrup depending on group.

SETTING: College of Medicine of the University of Lagos Medical Microbiology and Parasitology Laboratory. SUBJECTS: One hundred and twenty male and female albino mice aged 10-12 weeks with an average weight of 25 grams.

MAIN OUTCOME MEASURES: The herbal extract was effective, preventing the development of parasitaemia in the prophylactic group of mice. RESULTS: After intraperitoneal inoculation of Plasmodium yoelii nigeriensis, a prepatent period of two days was observed before parasitaemia was established in all but the prophylactic group of mice. Induced infection was promptly aborted with oral chloroquine treatment in group C, while in groups A and D, infection terminated fatally. Group B mice appeared normal throughout the duration of investigation with 100% survival rate.

CONCLUSION: ‘Agbo-Iba’ extract has some prophylactic action against malaria induced in mice with no apparent significant side effects. PMID: 12638827 East Afr Med J 2002 May;79(5):237-41

In-vitro sensitivity of Plasmodium falciparum to chloroquine, halofantrine, mefloquine and quinine in Madagascar. Randrianarivelojosia M, Ratsimbasoa A, Randrianasolo L, Randrianarijaona A, Jambou R. Unite d’Immunologie, Institut Pasteur de Dakar BP 220 Dakar, Senegal.

OBJECTIVE: To determine how sensitive Plasmodium falciparum is to the major antimalarial drugs in Madagascar.

DESIGN: Assessment of Plasmodium falciparum isolates sensitivity to antimalarials, by use of the in-vitro radioisotope method.

SETTING: Ankazobe and Saharevo in the foothill areas; and Toamasina and Tolagnaro in the coastal areas (between January 1998 and November 1999).

SUBJECTS: Primary Plasmodium falciparum isolates from patients with uncomplicated malaria attack.

RESULTS: Between January 1998 and November 1999, of the 293 in-vitro tests done with at least one antimalarial, 70% (205/293) were interpretable. As there was no significant difference between results from the four study sites, the data have been expressed as a whole. All of the successfully tested isolates were sensitive to halofantrine (n = 56) and to quinine (n = 199), 5.8% (12/205) of the isolates were resistant to chloroquine and 2% (4/199) to mefloquine. The geometric mean IC50 was 0.3 microg/L for halofantrine (95% CI = 0.1-0.4 microg/L); 9.4 microg/L for chloroquine (95% CI = 7.3-10.8 microg/L); 3.8 microg/L for mefloquine (95% CI = 3.3-4.3 microg/L); and 26.8 microg/L for quinine (95% CI = 24.3-29.4 microg/L). The low positive correlation found between halofantrine and chloroquine IC50s (n = 56; r = 0.41, P = 0.002) suggests a risk of cross-resistance between these two drugs. CONCLUSION: The degree and frequency of chloroquine resistance in-vitro is stationary in Madagascar compared to previous results during the last decade. The in-vitro sensitivity of P. falciparum to quinine, mefloquine and halofantrine encourages the use of these drugs as alternative in case of chloroquine treatment failure. Nevertheless, it is important to maintain and to extend malaria and drug sensitivity surveillance in Madagascar. PMID: 12638806 Malar J 2003 Feb 17;2(1):2

Observations on the swarming and mating behaviour of Anopheles funestus from southern Mozambique. Charlwood J, Thompson R, Madsen H. Danish Bilharziasis Laboratory, 1-D Jaergersborg Alle, DK2920 Charlottenlund, Denmark. Email: [email protected]

BACKGROUND: Control of malaria by the release of genetically modified mosquitoes refractory to transmission is now becoming a possibility. In many areas of Africa, Anopheles gambiae is found together with an equally important vector, An. funestus. Given their sympatry and the likelihood of a similar mating period some aspects of the mating behaviour of An. gambiae s.l. and An. funestus are likely to differ. We therefore attempted to characterise the swarming behaviour of An. funestus and to determine if any aspects of the observed behaviour differed from that recorded for the M form of An. gambiae from Sao Tome.

METHODS: In March – May 2002 the swarming, mating, house exiting and resting behaviour of Anopheles funestus was studied by direct observation in Mozambique. Swarming males and insects in copula were collected by sweep net. Wing lengths of males collected resting, exiting houses, swarming and mating were measured and the wingbeat frequency distribution of individual insects, in free flight confined inside netting covered paper cups, was also determined. RESULTS: Mono-specific swarms occurred at sunset in relatively open areas close to houses used for resting. Mating pairs were seen 11 PlusMinus; 3.7 min after the start of swarming. The number of total pairs observed being inversely proportional to the time difference between the start of swarming and the first pairing. The great majority of females mated before feeding. Male or female size did not appear to affect mating success or other behaviours. During the study, ambient temperatures decreased and female, but not male, wing size increased. At 516 Hz, the flight tone of female An. funestus was similar to the 497 Hz of the local An. gambiae. Males dispersed if light or dark artificial horizontal markers were placed underneath naturally occurring swarms.

CONCLUSION: Differential response to markers would be sufficient for swarming in An. funestus and An. gambiae s.l. to occur in distinct sites. PMID: 12636875 Parasitology 2003 Feb;126(Pt 2):103-12

The effects of host immunity on virulence-transmissibility relationships in the rodent malaria parasite Plasmodium chabaudi. Mackinnon MJ, Read AF. Institute of Cell, Animal and Population Biology, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland. Email: [email protected]

Here we examined the impact of host immunity on relationships between parasite virulence, transmission rate, intrinsic growth rate and host recovery rate in the rodent malaria parasite, Plasmodium chabaudi. Groups of naive and immunized mice were infected with 1 of 10 cloned lines of parasites and their infection dynamics were monitored for 19 days. We found that (1) host immunity reduced the growth rate, virulence, transmission rate and infection length, with a consequent 3-fold reduction in life-time transmission potential, (2) clone means for these traits ranked similarly across naive and immunized mice, (3) regression slopes of transmission potential on growth rate, virulence and infection length were similar in naive and immunized mice, (4) virulence and infection length were positively correlated in immunized but not naive mice, and (5) for a similar level of parasite growth rate and virulence, transmission potential and infection length were lower in immunized than naive mice. Thus host immunity reduced all these fitness traits in a manner consistent with direct parasite-driven biological links among them. These results support the basic assumption underlying our theory that predicts that anti-disease vaccines will select for higher virulence in those microparasites for which virulence is integrally linked to transmission. PMID: 12636347 Pediatr Infect Dis J 2003 Mar;22(3):251-256

Safety and therapeutic efficacy of artesunate suppositories for treatment of malaria in children in Papua New Guinea. Karunajeewa HA, Kemiki A, Alpers MP, Lorry K, Batty KT, Ilett KF, Davis TM.

BACKGROUND Although suppositories of artemisinin derivatives may be a valuable option for treatment of malaria in children when circumstances prevent oral and parenteral therapy, few confirmatory data have been published.METHODS We assessed the safety and efficacy of rectal artesunate in 47 children ages 5 to 10 years with uncomplicated malaria acquired in a hyperendemic area of Papua New Guinea. Thirty were symptomatic and had parasitemia >2000/&mgr;l (Group 1), 12 had and either a parasitemia <2000/&mgr;l or minimal/no symptoms (Group 2) and 5 had (Group 3). Each child received rectal artesunate 10 to 15 mg/kg at 0 and 12 h. After monitoring for 24 h, chloroquine plus sulfadoxine/pyrimethamine was given, and the patient discharged.

RESULTS Artesunate suppositories were well-tolerated. After 24 h only one child (from Group 1) had persistent parasitemia, and only one (from Group 3) had not defervesced. These two children received intramuscular quinine and recovered uneventfully. Three Group 2 children redeveloped fever and tachycardia at 24 h, but each responded to simple supportive measures and remained aparasitemic.

CONCLUSIONS Intrarectal artesunate is safe, effective initial treatment for uncomplicated malaria in children. A transient fever spike can sometimes occur after parasite clearance. We recommend that children with uncomplicated malaria receive two doses of >/=10 mg/kg rectal artesunate within the first 24 h. PMID: 12634587 Int J Parasitol 2003 Feb;33(2):175-83

Influence of CD4(+)CD25(+) T cells on Plasmodium berghei NK65 infection in BALB/c mice. Long TT, Nakazawa S, Onizuka S, Huaman MC, Kanbara H. Department of Protozoology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.

CD4(+) T cells co-expressing CD25 (CD4(+)CD25(+) T cells) have been identified as immunoregulatory suppressors modulating autoimmune response. Beside that, autoimmune response was supposed to be associated with malaria infection. Based on these data, we hypothesised that CD4(+)CD25(+) T cells may influence protective immunity to malaria parasites, while suppressing autoimmune response arising throughout the course of malarial infection. To test this possibility, we evaluated the kinetics of CD4(+)CD25(+) T cells during malaria infection and investigated the influence of CD25 depletion by anti-mouse CD25 monoclonal antibody (PC61) on the infection, using a mouse model of premunition to Plasmodium berghei NK65 malaria. The results showed that, during exacerbation of P. berghei NK65 infection, the proportion of CD4(+)CD25(+) T cells among CD4(+) T cells decreased, although that of CD4(+) T cells increased. CD25 depletion clearly delayed the growth of parasitaemia during parasite challenge, particularly in immunised mice. These findings demonstrated that CD4(+)CD25(+) T cells are able to influence protective immunity underlying premunition to P. berghei NK65 parasites. PMID: 12633655 Parasitol Res 2003 Mar;89(5):371-4

Design and development of an immunosensor for the detection of malaria in field conditions. Mya M, Saxena K, Roy A, Roy B. Centre for Biomedical Engineering, Indian Institute of Technology, New Delhi 110016, India.

Eradication of malaria in Southeast Asian countries is still a distant goal, due to the absence of a simple, rapid and inexpensive diagnostic technique. Here, an immunosensor for the photometric detection of malaria, the malaria-detecting immunosensor (MDI), is developed to detect Plasmodium falciparum malarial antibodies in human blood. The method uses the principle of laser light-scattering by latex bead agglutinates in media monitored by a light-detecting device. Agglutination is induced by mixing antigen-coated latex beads with serum antibodies. Immunoreactions are measured in terms of the Tyndall effect in the transmitted beam detected by photodiodes. MDI sensitivity and specificity are compared with the results of enzyme-linked immunoabsorbent assay and laser light-scattering immunoassay techniques, which show that it is a good and sensitive monitoring device. Parasitol Res 2003 Mar;89(5):354-7

Comparison of three antigen detection tests for diagnosis and follow-up of falciparum malaria in travellers returning to Berlin, Germany. Grobusch MP, Hanscheid T, Gobels K, Slevogt H, Zoller T, Rogler G, Teichmann D. Department of Parasitology, Institute of Tropical Medicine, Eberhard Karls University, Wilhelmstrasse 27, 72074 Tuebingen, Germany, Email: [email protected]

We determined the sensitivity and specificity of three rapid immunochromatographic malarial antigen detection test systems (RDTs) for the detection of Plasmodium falciparumand assessed the quality of follow-up results. ParaSight-F and ICT Malaria detect histidine-rich protein-2 (HRP-2), whereas OptiMal detects plasmodial lactate dehydrogenase (pLDH). ParaSight-F performed with 95.1% sensitivity and 97.1% specificity (554 patients tested of whom 144 had falciparum malaria). ICT Malaria performed with 95.7% sensitivity and 99.2% specificity (718 patients tested of whom 184 had falciparum malaria). OptiMal performed with 76.2% sensitivity and 99.7% specificity (539 patients tested of whom 130 had falciparum malaria). In follow-up investigations, HRP-2 did not appear to be a useful antigen due to its long half-life, whereas pLDH offers a reasonable correlation with the presence of viable parasites in those cases initially detected. We therefore conclude that a combination of both antigens might be the best option for creating a reliable RDT for the diagnosis of falciparum malaria. J Pharm Pharmacol 2003 Feb;55(2):193-8

Therapeutic equivalence of a low dose artemisinin formulation in falciparum malaria patients. Wong JW, Yuen KH, Nagappan S, Shahul WS, Ho SS, Gan EK, Toh WT. School of Pharmaceutical Sciences, University of Science Malaysia, Penang, Malaysia.

We have evaluated the therapeutic equivalence of a beta-cyclodextrin-artemisinin complex at an artemisinin dose of 150 mg, with a commercial reference preparation, Artemisinin 250 at a recommended dose of 250 mg. One hundred uncomplicated falciparum malarial patients were randomly assigned to orally receive either beta-cyclodextrin-artemisinin complex (containing 150 mg artemisinin) twice daily for five days or the active comparator (containing 250 mg artemisinin) twice daily for five days. The patients were hospitalized for seven days and were required to attend follow up assessments on days 14, 21, 28 and 35. All patients in both treatment groups were cured of the infection and achieved therapeutic success. At day seven of treatment, all patient blood was clear of the parasites and the sublingual temperature of all patients was less than 37.5 degrees C. Moreover, the parasite clearance time in both treatment groups was similar, being approximately three days after initiation of treatment. Comparable plasma artemisinin concentrations were observed between patients in both treatment groups at 1.5 and 3.0 h, although slightly higher levels were obtained with patients in the beta-cyclodextrin-artemisinin complex-treated group. The beta-cyclodextrin-artemisinin complex at a dose of 150 mg artemisinin was therapeutically equivalent to 250 mg Artemisinin 250. Additionally, patients receiving beta-cyclodextrin-artemisinin complex showed less variability in their plasma artemisinin concentrations at 1.5 h post-dosing, which suggested a more consistent rate of drug absorption. PMID: 12631411 Trop Med Int Health 2003 Mar;8(3):242-50

Hospital costs of high-burden diseases: malaria and pulmonary tuberculosis in a high HIV prevalence context in Zimbabwe. Hongoro C, McPake B. Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, UK.

This paper explores the measurement of hospital costs and efficiency in a context where data is scarce, incomplete or of poor quality. It argues that there is scope for using tracers to examine and compare hospital cost structures and relative efficiency in such contexts. Two high-burden diseases, malaria and pulmonary tuberculosis, are used as tracers to calculate the average costs of inpatient care at selected tertiary hospitals. This study shows that it is feasible to prospectively collect cost data for specific diseases and explore in detail both patient cost distribution and susceptible areas for efficiency improvement. The present study found that the critical source of efficiency variation in public hospitals in Zimbabwe lies in the way hospital beds are used. Trop Med Int Health 2003 Mar;8(3):202-3

Clinical efficacy of chloroquine in young children with uncomplicated falciparum malaria – a community-based study in rural Burkina Faso. Muller O, Traore C, Kouyate B. Department of Tropical Hygiene and Public Health of the Ruprecht-Karls-University Heidelberg, Heidelberg, Germany Centre de Recherche en Sante de Nouna, Nouna, Burkina Faso.

We report on a 14-day study on the efficacy of chloroquine for treating uncomplicated falciparum malaria in young children of a malaria holoendemic area in rural Burkina Faso. In this community-based study, the overall treatment failure rate was 12/120 (10%), with no differences between villages. This supports the evidence for a still sufficient efficacy of chloroquine in north-western Burkina Faso. PMID: 12631308 Trop Med Int Health 2003 Mar;8(3):196-201 A health facility based case-control study of effectiveness of insecticide treated nets: potential for selection bias due to pre-treatment with chloroquine. Webster J, Chandramohan D, Freeman T, Greenwood B, Kamawal AU, Rahim F, Rowland M. London School of Hygiene and Tropical Medicine, UK HealthNet International, Peshawar, Pakistan. Case control studies offer an attractive way to assess the effectiveness of insecticide treated nets (ITN) under programme conditions but have the drawback of being susceptible to bias in the choice of controls. We evaluated the potential for pre-treatment with chloroquine to result in misclassification of cases and controls and affect estimates of ITN effectiveness in case control studies in urban and rural clinics in Eastern Afghanistan. During the one-month study, use of ITN showed no effect against malaria in the urban clinic (adjusted odds ratio OR 1.08; 95% CI 0.73-1.6) and the protective effect seen in the rural clinic was not significant (OR 0.62; 95% CI 0.2-2.4). Levels of pre-treatment were high in both clinics: 24% in urban and 19% in rural clinic attenders. In the urban clinic attenders the level of pre-treatment between bed net users and non-users was not significantly different (OR 1.07, 95% CI 0.70-1.64); therefore the misclassification of cases as controls did not introduce any selection bias. Amongst rural clinic attenders, bed net users were less likely to pre-treat with chloroquine than users (OR 0.33, 95% CI 0.14-0.77); this introduced a selection bias that resulted in an underestimation of the effectiveness of bed nets. Case control studies using health facility data are liable to selection bias especially in areas of high pre-treatment rates with chloroquine. Generalisation of results over a wide geographic region, or between urban and rural settings, may not be appropriate. PMID: 12631307 Trans R Soc Trop Med Hyg 2002 Nov-Dec;96(6):674-6

Highly pyrimethamine-resistant alleles of dihydrofolate reductase in isolates of Plasmodium falciparum from Tanzania. Hastings MD, Bates SJ, Blackstone EA, Monks SM, Mutabingwa TK, Sibley CH. Department of Genetics, Box 357360, University of Washington, Seattle, WA 98195-7360, USA.

In 2000 we used a sensitive technique to examine 9 isolates from malaria patients in Muheza, Tanzania who had failed treatment with sulfadoxine-pyrimethamine (SP). Three isolates carried, at low levels, the leucine to isoleucine change at amino acid 164 that is associated with clinical failure of SP. Numerous other highly resistant alleles were also observed. PMID: 12630380 Bioorg Med Chem 2003 Apr;11(7):1235-46 New potent C(2)-Symmetric malaria plasmepsin I and II inhibitors. Oscarsson K, Oscarson S, Vrang L, Hamelink E, Hallberg A, Samuelsson B. Department of Organic Chemistry, Arrhenius Laboratory, Floor 6, Stockholm University, S-106 91, Stockholm, Sweden A series of malaria plasmepsin (Plm) I and II inhibitors containing a C(2)-symmetric core structure have been synthesised and tested for protease inhibition activity. These compounds can be prepared using a straightforward synthesis involving a phenol nucleophilic ring opening of a diepoxide. Exemplar compounds synthesised exhibited remarkable inhibitory activity against both Plm I and II, notably 15c with K(i) values of 2.7nM and 0.25nM respectively, as well as showing >100-fold selectivity against Cathepsin D. PMID: 12628651 Biochimie 2002 Dec;84(12):1181-8

Protection against experimental P. falciparum malaria is associated with short AMA-1 peptide analogue alpha-helical structures. Cubillos M, Salazar LM, Torres L, Patarroyo ME. Fundacion Instituto de Inmunologia de Colombia (FIDIC), Carrera 50, No. 26-00 Bogota, Colombia.

Apical membrane antigen-1 (AMA-1) is an integral Plasmodium falciparum malaria parasite membrane protein. Peptides having high activity binding to human red blood cells have been identified in this protein. One of them, peptide 4325, with the amino acid sequence MIKSAFLPTGAFKADRYKSH, for which critical binding residues have already been defined (underlined), is conserved and non-immunogenic. Its critical binding residues were changed for amino acids having similar mass but different charge to change such immunological properties. These changes rendered some peptides immunogenic and protective against experimental challenge in Aotus monkeys. Three-dimensional models of peptide 4325 and its analogues, 20032 and 20034, were calculated from NMR experiments with distance geometry and restrained molecular dynamic methods. Non-immunogenic, non-protective peptide 4325 showed differences in its secondary structure with respect to protective, immunogenic peptides 20032 and 20034. Such data suggest that these modifications could have converted non-immunogenic peptides into immunogenic, protective ones, making them excellent candidates for a multi-component subunit synthetic malaria vaccine. PMID: 12628294 [PubMed – in process] J Immunol 2003 Mar 15;170(6):3195-203

The Dendritic Cell-Specific Chemokine, Dendritic Cell-Derived CC Chemokine 1, Enhances Protective Cell-Mediated Immunity to Murine Malaria. Bruna-Romero O, Schmieg J, Del Val M, Buschle M, Tsuji M. Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010. Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain. Intercell AG, Vienna, Austria.

Cell-mediated immunity plays a crucial role in the control of many infectious diseases, necessitating the need for adjuvants that can augment cellular immune responses elicited by vaccines. It is well established that protection against one such disease, malaria, requires strong CD8(+) T cell responses targeted against the liver stages of the causative agent, Plasmodium spp. In this report we show that the dendritic cell-specific chemokine, dendritic cell-derived CC chemokine 1 (DC-CK1), which is produced in humans and acts on naive lymphocytes, can enhance Ag-specific CD8(+) T cell responses when coadministered with either irradiated Plasmodium yoelii sporozoites or a recombinant adenovirus expressing the P. yoelii circumsporozoite protein in mice. We further show that these enhanced T cell responses result in increased protection to malaria in immunized mice challenged with live P. yoelii sporozoites, revealing an adjuvant activity for DC-CK1. DC-CK1 appears to act preferentially on naive mouse lymphocytes, and its adjuvant effect requires IL-12, but not IFN-gamma or CD40. Overall, our results show for the first time an in vivo role for DC-CK1 in the establishment of primary T cell responses and indicate the potential of this chemokine as an adjuvant for vaccines against malaria as well as other diseases in which cellular immune responses are important. PMID: 12626578

Ann Trop Med Parasitol 2002 Dec;96 Suppl 2:143-52 Limitation and facilitation in the vectors and other aspects of the dynamics of filarial transmission: the need for vector control against Anopheles-transmitted filariasis. Pichon G. Institut de Recherche pour le Developpement (IRD), Laboratoire d’Informatique Appliquee, 32 Avenue Henri Varagnat, 93143 Bondy Cedex, France.

In certain filaria-mosquito combinations, the number of infective, third-stage larvae (L(3)) that develop in a mosquito is not proportional to the number of microfilariae (mff) ingested by that mosquito. As the number of mff ingested increases, the yield of L(3) per microfilaria may either increase (in a process known as ‘facilitation’) or decrease (in a process known as ‘limitation’). Each ingested microfilaria that is successful (in terms of reaching the haemocoel) increases (facilitation) or decreases (limitation) the ‘permeability’ of the stomach wall for the next microfilaria. Limitation is seen in some culicine mosquitoes, especially the Aedes spp. that transmit Wuchereria bancrofti, which, in consequence, become relatively more efficient as vectors as they ingest fewer mff. This phenomenon makes the interruption of filarial transmission by Aedes spp. particularly difficult. As the survival of anopheline mosquitoes is adversely affected by filarial infection, the use of mass drug administrations (MDA) to reduce the prevalence and intensity of microfilaraemias may increase the mean lifespan of some of the local Anopheles species. If these same species also act as vectors of malarial parasites, effective, drug-based control of W. bancrofti may worsen the problem posed by malaria. Therefore, wherever malaria and bancroftian filariasis are co-endemic and caused by parasites transmitted by the same species of mosquito, MDA should be augmented by interventions (use of bednets or house-spraying) against adult Anopheles. PMID: 12625927 East Afr Med J 2002 Sep;79(9):485-90

Impact of cattle keeping on human biting rate of anopheline mosquitoes and malaria transmission around Ziway, Ethiopia. Seyoum A, Balcha F, Balkew M, Ali A, Gebre-Michael T. Institute of Pathobiology, Faculty of Medicine, Addis Ababa University, P.O. Box 1176, Addis Ababa, Ethiopia.

OBJECTIVE: To assess the impact of livestock keeping on the human biting rate (HBR) of anopheline mosquitoes and malaria transmission around Ziway in the middle course of the Ethiopian Rift Valley.

DESIGN: As a passive experiment, man landing captures were done in homesteads with mixed dwelling, separate cattle shed and without livestock; and as an active experiment, captures were in experimental tukuls (huts) of cattle, goats, and without livestock. Parasite and spleen rates of children were compared among those residents under variable living conditions mentioned for passive experiment.

SUBJECTS: For entomological study, human-baits were used for man-landing captures of mosquitoes. Study subjects for parasitological and clinical studies were children below 10 years old.

MAIN OUTCOME MEASURES: Human-biting rate (HBR) of anopheline mosquitoes; and the parasite and spleen rates of the study subjects in different living conditions. RESULTS: In the passive experiment, the mean HBR of Anopheles arabiensis in mixed dwelling, separate cattle shed and without livestock was 8.45, 4.64 and 5.97, respectively. Similarly, the HBR of An. pharoensis was 2.88, 1.79 and 1.61, respectively. In the active experiment, the mean HBR of An. arabiensis in tukuls with cattle, goats, and without livestock was 3.50, 3.38 and 1.43 respectively; while that of An. pharoensis was 0.37, 0.70 and 0.55 respectively. Parasitologically, mean parasite rates of 26.67%, 15.05% and 23.85% were, respectively, recorded from children living under the above conditions stated for passive experiment. Similarly, the mean spleen rates of 50.0%, 26.9%, and 47.37% were recorded, respectively.

CONCLUSION: These observations in the present study indicate that the presence of cattle in homesteads tends to increase the man biting rate of An. arabiensis, although differences in the mean HBR of vector mosquitoes were not statistically significant for all groups. In contrast, cattle keeping in separate cattle sheds outside of the human dwellings tends to reduce the man biting rate of An. arabiensis and malaria transmission in the study area. PMID: 12625690 East Afr Med J 2002 Sep;79(9):480-4

Molecular markers in epidemiological monitoring of the spread of resistance to antimalarials: a review. Nyamwange CI, Nyamogoba H. Department of Medical Microbiology and Parasitology, Faculty of Health Sciences, Moi University, P.O. Box 4606, Eldoret, Kenya.

OBJECTIVE: To review the prevalence and distribution of resistance to chloroquine and pyrimethamine-sulphadoxine combination and the use of molecular markers for monitoring the spread of the resistance.

DATA SOURCES: Literature search on compact disk-read only memory (CD-ROM), Medline and Internet, using the key words: Malaria and epidemiology, malaria and resistance, sulphadoxine-pyrimethamine resistance and chloroquine resistance. Some articles were manually reviewed. STUDY SELECTION: Relevant studies or articles on resistance to chloroquine, sulphadoxine pyrimethamine combination and other antimalarials and molecular resistance markers from various sources are included in the review.

DATA EXTRACTION: From individual study or articles.

DATA SYNTHESIS: Information on antimalarial resistance is harmonised under the headings; Introduction, Prevalence and distribution of resistance to antimalarials, Use of molecular markers for epidemiological monitoring of antimalarial resistance.

CONCLUSION: The spread and status of resistance to sulphadoxine-pyrimethamine (SP) and chloroquine should be monitored constantly in major health facilities. This will not only detect the emergence of resistance to these drugs but also generate information on the extent of resistance to these antimalarials. Mutations in the dhfr and dhps genes can be used as markers in SP resistance surveilance while the presence of pfcrt mutations thought to confer resistance should also be analysed to ascertain whether they truly correlate to the resistance patterns that have been observed in various malarious regions. Little is known on the interaction and exact role(s) of PfCRT protein in conferring the resistance trait. PMID: 12625689 [PubMed – in process]

Trans R Soc Trop Med Hyg 2002 Nov-Dec;96(6):683-4 Comparison of tafenoquine (WR238605) and primaquine in the post-exposure (terminal) prophylaxis of vivax malaria in Australian Defence Force personnel. Nasveld P, Kitchener S, Edstein M, Rieckmann K. Australian Defence Force Combined Health Element, Loloho, North Solomons Province, Papua New Guinea.

On return from duty in North Solomons Province (including Bougainville Island), Papua New Guinea, 586 Australian Defence Force personnel received either primaquine (14-d) or tafenoquine (3-d) post-exposure malaria prophylaxis. Within 12 months, 6 of the 214 volunteers receiving primaquine and 7 of 378 receiving tafenoquine had developed vivax malaria. Overall, volunteers preferred the shorter course of tafenoquine. PMID: 12625150 Trans R Soc Trop Med Hyg 2002 Nov-Dec;96(6):670-3 Efficacy of amodiaquine for uncomplicated Plasmodium falciparum malaria in Harper, Liberia. Checchi F, Balkan S, Vonhm BT, Massaquoi M, Biberson P, Eldin de Pecoulas P, Brasseur P, Guthmann JP. Malaria Control Program, Ministry of Health and Social Welfare, Monrovia, Liberia. In the face of spreading chloroquine and sulfadoxine-pyrimethamine (SP) resistance, amodiaquine remains a cheap and efficacious alternative for treating uncomplicated Plasmodium falciparum malaria in many settings. In Harper, south-eastern Liberia, a previous study we conducted showed very high levels of resistance to both chloroquine and SP. In 2001, in an effort to look for possible alternatives, we measured in the same setting the efficacy of amodiaquine in a 28-d study in vivo, with results corrected by polymerase chain reaction genotyping to distinguish recrudescences from reinfections. In total, 107 children were included in the study and received a 3-d supervised course of 25 mg/kg amodiaquine. Of these, 81 were analysable at day 28. The overall failure rate was 19.8% (95% CI 11.7-30.1%) considering both parasitological and clinical outcomes. These results provide hitherto missing data on amodiaquine in Liberia, and confirm that the drug may still be efficacious in settings where chloroquine and SP are failing. We recommend the introduction of amodiaquine in association with artesunate as a first-line antimalarial in Harper. PMID: 12625148 [PubMed – in process] Trans R Soc Trop Med Hyg 2002 Nov-Dec;96(6):664-9

High Plasmodium falciparum resistance to chloroquine and sulfadoxine-pyrimethamine in Harper, Liberia: results in vivo and analysis of point mutations. Checchi F, Durand R, Balkan S, Vonhm BT, Kollie JZ, Biberson P, Baron E, Le Bras J, Guthmann JP. Laboratoire de Parasitologie-Mycologie, Hopital Bichat-Claude Bernard, 46 rue Henri Huchard, 75877 Paris, France.

In Liberia, little information is available on the efficacy of antimalarials against Plasmodium falciparum malaria. We measured parasitological resistance to chloroquine and sulfadoxine-pyrimethamine (SP) in Harper, south-west Liberia in a 28-d study in vivo. A total of 50 patients completed follow-up in the chloroquine group, and 66 in the SP group. The chloroquine failure rate was 74.0% (95% confidence interval [95% CI] 59.7-85.4%) after 14 d of follow-up and 84.0% (95% CI 70.9-92.8%) after 28 d (no polymerase chain reaction [PCR] analysis was performed to detect reinfections in this group). In the SP group, the failure rate was 48.5% (95% CI 36.2-61.0%) after 14 d and 69.7% (95% CI 57.1-80.4%) after 28 d, readjusted to 51.5% (95% CI 38.9-64.0%) after taking into account reinfections detected by PCR. Genomic analysis of parasite isolates was also performed to look for point mutations associated with resistance. Genotyping of parasite isolates revealed that all carried chloroquine-resistant K-76T mutations at gene pfcrt, whereas the triple mutation (S108N, N511, C59R) at dhfr and the A437G mutation at dhps, both associated with resistance to SP, were present in 84% and 79% of pretreatment isolates respectively. These results seriously question the continued use of chloroquine and SP in Harper and highlight the urgency of making alternative antimalarial therapies available. Our study confirms that resistance to chloroquine may be high in Liberia and yields hitherto missing information on SP. PMID: 12625147 [PubMed – in process] Trans R Soc Trop Med Hyg 2002 Nov-Dec;96(6):660-3

Reassessment of the resistance of Plasmodium falciparum to chloroquine in Gabon: implications for the validity of tests in vitro vs. in vivo. Borrmann S, Binder RK, Adegnika AA, Missinou MA, Issifou S, Ramharter M, Wernsdorfer WH, Kremsner PG. Medical Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon. Email: [email protected]

Increasing resistance of Plasmodium falciparum to antimalarial drugs presents a major risk factor for people living in endemic areas of tropical Africa. In Lambarene, Gabon, regular surveillance of chloroquine sensitivity of P. falciparum in vitro has been carried out since 1992 using the WHO standard microtest. Results indicated that from 1994 onwards chloroquine resistance in vitro decreased significantly and that by 2000, about 70% of parasite isolates seemed to be sensitive to chloroquine in vitro. In 2001, we conducted a clinical study to reassess the efficacy of chloroquine in vivo for the treatment of uncomplicated P. falciparum malaria. Twenty-six patients aged 4-15 years were included in this study. Most unexpectedly, the study demonstrated high-grade resistance to chloroquine in vivo (failure rate on day 28 of 100%). As a consequence, tests of parasite susceptibility to chloroquine in vitro were repeated using the same protocol except for the replacement of previously used commercially available predosed WHO culture plates by independently dosed plates. All tested P. falciparum isolates were highly resistant to chloroquine, correlating well with our clinical findings. We concluded that high level resistance of P. falciparum to chloroquine persists in the study area. Neglect or absence of quality controls of essential test material can lead to invalid study results and wrong conclusions and should always be suspected in the case of major fluctuations in the sensitivity patterns of an antimalarial drug in vitro. In addition, our results highlight the supreme value of tests in vivo in providing reliable estimates of the efficacy of an antimalarial in a specific area. PMID: 12625146 Trans R Soc Trop Med Hyg 2002 Nov-Dec;96(6):655-9

A randomized, double-blind study on the efficacy and safety of a practical three-day regimen with artesunate and mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria in Africa. Massougbodji A, Kone M, Kinde-Gazard D, Same-Ekobo A, Cambon N, Mueller EA. Centre National Hospitalier et Universitaire, Cownou, Benin.

A randomized, double-blind, parallel-group study in 104 hospitalized patients with acute, uncomplicated Plasmodium falciparum malaria was performed in West and Central Africa from March to July 2001. Patients were randomized to receive simultaneous dosing (artesunate 200 mg/d plus mefloquine 250 mg/d from the first to the third day [investigational group]) or sequential dosing (artesunate 200 mg/d for 3 d plus mefloquine 250 mg on the second and 500 mg on the third day [reference group]). Patients were followed-up for 28 d, and clinical and parasitological outcomes were assessed. The 14-d cure rate was 100% in the investigational group and 98% in the reference group with no recrudescence until day 28. Mean times to fever and parasite clearance were similar between the 2 groups (32 h vs. 26 h and 45 h vs. 48 h) and tolerability was good in both groups. The number of patients with vomiting was statistically significantly lower in the investigational group compared to the reference group (3.8% vs. 19.2%, P = 0.014). A 3-d once-daily co-administration of artesunate and mefloquine starting on day one offers a practical dosing regimen, which is highly effective and well tolerated in patients with uncomplicated P. falciparum malaria. PMID: 12625145 Trans R Soc Trop Med Hyg 2002 Nov-Dec;96(6):647-8

Case report: severe acute symptomatic hyponatraemia in falciparum malaria. Ustianowski A, Schwab U, Pasvol G. Department of Infection and Tropical Medicine, Faculty of Medicine, Imperial College, Lister Unit, Northwick Park Hospital, Harrow, Middlesex HA1 3UJ, UK.

Hyponatraemia is a common finding in malaria, but rarely appears to be of clinical significance. We describe a case of acute, profound, hyponatraemia with confusion and convulsions developing in the context of seemingly uncomplicated Plasmodium falciparum malaria. We draw attention to this rarely reported and poorly documented life-threatening complication and review the limited literature on the subject. PMID: 12625142 Trans R Soc Trop Med Hyg 2002 Nov-Dec;96(6):644-6

Haemozoin as a marker of placental parasitization. McGready R, Brockman A, Cho T, Levesque MA, Tkachuk AN, Meshnick SR, Nosten F. Shoklo Malaria Research Unit, P.O. Box 46, Mae Sot 63110, Thailand. Email: [email protected]

Both Plasmodium vivax and P. falciparum malaria can cause the delivery of low birthweight babies. In this report, we have quantitated haemozoin levels in placentas from women living on the Thai-Burmese border in a region of low transmission for both P. falciparum and P. vivax malaria from June 1995 to January 2000. P. falciparum malaria infections during pregnancy lead to the accumulation of haemozoin (malaria pigment) in the placenta, especially in infections near term and in primigravid pregnancies. Haemozoin concentration was not associated with adverse birth outcomes. Women with P. vivax infections during pregnancy do not have measurable levels of placental haemozoin suggesting that P. vivax-infected erythrocytes do not accumulate in the placenta as much as P. falciparum-infected ones. PMID: 12625141 Trans R Soc Trop Med Hyg 2002 Nov-Dec;96(6):620-6

Anopheline vectors and malaria transmission in eastern Afghanistan. Rowland M, Mohammed N, Rehman H, Hewitt S, Mendis C, Ahmad M, Kamal M, Wirtz R. HealthNet International, Peshawar, Pakistan. Email: [email protected]

Anopheline vectors and malaria transmission were studied in 2 river-irrigated, rice-growing districts of eastern Afghanistan from May 1995 to December 1996. Clinical malaria was monitored in 12 rural villages (population 14,538) by passive case detection at local clinics. Adult mosquitoes were collected by space-spraying of living quarters and stables and by cattle bait catches. Mosquito head-thoraces (17,255 specimens) were tested for Plasmodium falciparum and P. vivax circumsporozoite protein (CSP) using enzyme-linked immunosorbent assay. The recorded incidence of P. vivax and P. falciparum was 199 and 41 episodes per 1000 person years, respectively. Twelve species of anopheline were recorded; Anopheles stephensi comprised 82% and A. culicifacies 5%. Eight species tested positive for CSP: A. stephensi, A. culicifacies, A. fluviatilus, A. annularis, A. pulcherrimus, A. maculatus, A. splendidus and A. superpictus. Among infected mosquitoes 46% were positive for P. falciparum, 45% for P. vivax VK-247, and 9% for P. vivax PV-210. Estimates of the feeding rates of infective vectors on humans indicated that A. stephensi would contribute 76% of infective bites, A. fluviatilis and A. pulcherrimus 7% each, and A. culicifacies and A. superpictus 3% each. The overall infective vector feeding rate correlated with the P. vivax incidence rate in the human population. The conventional view of A. culicifacies being the main rural vector and A. stephensi important only in urban settings needs to be reconsidered in western outreaches of the Indo-Pakistan subcontinent. PMID: 12625136 Trans R Soc Trop Med Hyg 2002 Nov-Dec;96(6):597-9

Mortality in a seven-and-a-half-year follow-up of a trial of insecticide-treated mosquito nets in Ghana. Binka FN, Hodgson A, Adjuik M, Smith T. Navrongo Health Research Centre, P.O. Box 114, Navrongo, Ghana.

A 17% efficacy in preventing all-cause mortality in children aged 6-59 months was previously reported from a cluster-randomized controlled trial of insecticide-treated mosquito nets (ITNs) carried out in the Kassena-Nankana District of northern Ghana from July 1993-June 1995. A follow-up until the end of 2000 found no indication in any age group of increased mortality in the ITN group after the end of the randomized intervention. These results should further encourage the use of ITNs as a malaria control tool in areas of high endemicity of Plasmodium falciparum. PMID: 12625130 Trans R Soc Trop Med Hyg 2002 Nov-Dec;96(6):593-6

Zooprophylaxis, artefact or reality? A paired-cohort study of the effect of passive zooprophylaxis on malaria in The Gambia. Bogh C, Clarke SE, Walraven GE, Lindsay SW. Danish Bilharziasis Laboratory, Jaegersborg Alle 1D, DK-2920 Charlottenlund, Denmark. Email: [email protected]

The World Health Organization has recommended the use of cattle for zooprophylaxis as a protective measure against malaria since 1982. However, concern has been raised about this practice, since some studies have shown that the presence of cattle may instead increase malaria prevalence. This study was designed to investigate the effect of passive zooprophylaxis on malaria in an area of moderate seasonal transmission in The Gambia, West Africa. The study was based on a paired-cohort of 204 children aged < 7 years, sleeping < 20 m or > 50 m from cattle, and surveys were done from 14 October to 2 December 1997. Entomological investigations showed that the presence of cattle did not alter the risk of malaria transmission in nearby houses. There was also no significant difference in the prevalence of Plasmodium falciparum between the 2 groups. Although the presence of cattle appeared to be protective against high parasitaemia, cattle were also associated with greater wealth of the children’s families. Conditional logistic regression analysis showed that the decreased risk of high parasitaemia in the group with cattle present was an artefact associated with the higher general wealth of the cattle owners. We concluded that zooprophylaxis is not an effective intervention method against malaria in settings similar to The Gambia. PMID: 12625129 Trans R Soc Trop Med Hyg 2002 Nov-Dec;96(6):586-92

Risk factors for malaria in pregnancy in an urban and peri-urban population in western Kenya. van Eijk AM, Ayisi JG, ter Kuile FO, Misore AO, Otieno JA, Rosen DH, Kager PA, Steketee RW, Nahlen BL. Kenya Medical Research Institute, Centre for Vector Biology and Control Research, Kisumu, Kenya. Email: [email protected]

To assess risk factors for malaria in pregnancy in Kisumu, western Kenya, we studied healthy women with an uncomplicated pregnancy of > or = 32 weeks attending the antenatal clinic in the Provincial Hospital. Between June 1996 and March 1999, malaria and human immunodeficiency virus (HIV) infection were examined in 5093 pregnant women: 20.1% of the women were parasitaemic and 24.9% were HIV-seropositive. 2502 women delivered in the hospital and a smear was obtained: the prevalence of placental malaria, maternal peripheral parasitaemia, and HIV infection was respectively 19.0%, 15.2% and 24.5%. HIV infection (risk ratio [RR] 1.58, 95% confidence interval [95% CI] 1.32-1.89), young age (< 21 years: RR 1.51, 95% CI 1.19-1.91), being a primigravidae (RR 1.41, 95% CI 1.05-1.88), a peri-urban residence (RR 1.50, 95% CI 1.21-1.88), and Luo ethnicity (RR 1.74, 95% CI 1.35-2.24) were risk factors for malaria at delivery. Use of sulfadoxine-pyrimethamine (SP), reported by 2.1% of the women, was a protective factor (RR 0.44, 95% CI 0.18-1.06). Results were similar in the third trimester. In this urban/peri-urban setting, preventing HIV infection, delaying the first pregnancy until after adolescence, and applying an effective antimalarial strategy such as intermittent therapy with SP will reduce the prevalence of malaria in pregnancy. PMID: 12625128

Clin Infect Dis 2003 Jan 15;36(Suppl 1):S4-10 The global impact of drug resistance. Howard DH, Scott RD 2nd, Packard R, Jones D. Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA. Email: [email protected]

Measuring the impact of drug resistance is an important step in understanding the scope of the problem and formulating policies to limit the emergence and spread of resistant organisms. Studies have focused on measuring the increased costs, morbidity, and mortality in patients with infections due to resistant versus susceptible organisms. These have generally found that resistance worsens outcomes. By focusing only on infected patients, however, they may understate the impact of resistance. It is important to recognize that resistance also affects the treatment of individuals with nonresistant organisms. In areas with high rates of resistance, physicians and governments have changed empiric therapy for malaria, tuberculosis, acute respiratory infections, and other diseases, increasing overall treatment costs. In some instances, these costs may exceed those attributable to treatment failure. PMID: 12516025

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