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EHP Library Malaria Bulletin No. 21: September 7-September 21, 2001

Social Sciences and Malaria

Trop Med Int Health 2001 Sep;6(9):677-87
Efficacy and cost-effectiveness of environmental management for malaria control.

Utzinger J, Tozan Y, Singer BH.

Office of Population Research, Princeton University, Princeton, USA; Woodrow Wilson School of Public and International Affairs, Princeton University, Princeton, USA.

Roll back malaria (RBM) aims at halving the current burden of the disease by the year 2010. The focus is on sub-Saharan Africa, and it is proposed to implement efficacious and cost-effective control strategies. But the evidence base of such information is scarce, and a notable missing element is the discussion of the potential of environmental management. We reviewed the literature and identified multiple malaria control programmes that incorporated environmental management as the central feature. Prominent among them are programmes launched in 1929 and implemented for two decades at copper mining communities in Zambia. The full package of control measures consisted of vegetation clearance, modification of river boundaries, draining swamps, oil application to open water bodies and house screening. Part of the population also was given quinine and was sleeping under mosquito nets. Monthly malaria incidence rates and vector densities were used for surveillance and adaptive tuning of the environmental management strategies to achieve a high level of performance. Within 3-5 years, malaria-related mortality, morbidity and incidence rates were reduced by 70-95%. Over the entire 20 years of implementation, the programme had averted an estimated 4173 deaths and 161 205 malaria attacks. The estimated costs per death and malaria attack averted were US$ 858 and US$ 22.20, respectively. Over the initial 3-5 years start-up period, analogous to the short-duration of cost-effectiveness analyses of current studies, we estimated that the costs per disability adjusted life year (DALY) averted were US$ 524-591. However, the strategy has a track record of becoming cost-effective in the longer term, as maintenance costs were much lower: US$ 22-92 per DALY averted. In view of fewer adverse ecological effects, increased sustainability and better uses of local resources and knowledge, environmental management - integrated with pharmacological, insecticidal and bednet interventions - could substantially increase the chances of rolling back malaria.

PMID: 11555434 [PubMed - in process]


Trop Med Int Health 2001 Sep;6(9):667-676
The impact of insecticide-treated bednets on malaria and anaemia in pregnancy in Kassena-Nankana district, Ghana: a randomized controlled trial.

Browne EN, Maude GH, Binka FN.

Department of Community Health, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; MRC Tropical Epidemiology Group, London School Hygiene and Tropical Medicine, UK; Navrongo Health Research Centre, Ministry of Health, Navrongo, Ghana.

The impact of insecticide-treated bednet use on malaria and anaemia in pregnancy was assessed, as a supplementary study, in a major WHO/TDR-supported bednet trial in northern Ghana between July 1994 and April 1995. The study area was divided into 96 clusters of compounds, with 48 clusters being randomly allocated to intervention. All pregnant women were included in the study but the focus was on primigravidae and secundigravidae. 1961 pregnant women were recruited into the study - 1033 (52.7%) in the treated bednet group and 928 (47.3%) in the no net group. 1806 (92.1%) had blood taken for malaria microscopy and haemoglobin determination in the third trimester. Pregnancy outcomes were reported for 847 women. The characteristics of women in intervention and control groups were comparable. The odds ratios, with 95% confidence interval (CI), for different study endpoints were, for Plasmodium falciparum parasitaemia - 0.89 (0.73, 1.08), for anaemia - 0.88 (0.70, 1.09), for low birthweight (LBW) - 0.87 (0.63, 1.19), indicating no benefit for treated bednet use. Effective net use by parity varied from 42% in primigravidae to 63% in multigravidae, in spite of free nets and insecticide impregnation. The main reasons for not using a net were warm weather and perceived absence of mosquito biting. Chloroquine use in pregnancy was low and comparable in both groups. Implications of findings for malaria control in pregnancy and further research are discussed.

PMID: 11555433 [PubMed - as supplied by publisher]

Trop Med Int Health 2001 Aug;6(8):614-23
Introducing insecticide-treated nets in the Kilombero Valley, Tanzania: the relevance of local knowledge and practice for an Information, Education and Communication (IEC) campaign.

Minja H, Schellenberg JA, Mukasa O, Nathan R, Abdulla S, Mponda H, Tanner M, Lengeler C, Obrist B.

Ifakara Health Research and Development Centre, Ifakara, Tanzania; Swiss Tropical Institute, Basel, Switzerland; Institute of Anthropology, University of Basel, Basel, Switzerland.

Since 1997 the WHO has been recommending an integrative strategy to combat malaria including new medicines, vaccines, improvements of health care systems and insecticide-treated nets (ITNs). After successful controlled trials with ITNs in the past decade, large-scale interventions and research now focus on operational issues of distribution and financing. In developing a social marketing approach in the Kilombero Valley in south-east Tanzania in 1996, a combination of qualitative and quantitative methods was employed to investigate local knowledge and practice relating to malaria. The findings show that the biomedical concept of malaria overlaps with several local illness concepts, one of which is called maleria and refers to mild malaria. Most respondents linked maleria to mosquitoes (76%) and already used mosquito nets (52%). But local understandings of severe malaria differed from the biomedical concept and were not linked to mosquitoes or malaria. A social marketing strategy to promote ITNs was developed on the basis of these findings, which reinforced public health messages and linked them with nets and insecticide. Although we did not directly evaluate the impact of promotional activities, the sharp rise in ownership and use of ITNs by the population (from 10 to > 50%) suggests that they contributed significantly to the success of the programme. Local knowledge and practice is highly relevant for social marketing strategies of ITNs.

PMID: 11555427 [PubMed - in process]

Am J Trop Med Hyg 2001 Sep;65(3):252-6
Health risk behaviors and health perceptions in the Peruvian Amazon.

Nawaz H, Rahman MA, Graham D, Katz DL, Jekel JF.

Department of Preventive Medicine, Griffin Hospital, Derby, Connecticut 06418, USA. Email: [email protected]
 
Behavioral health risk factor and health belief data for the indigenous population of the Peruvian Amazon are unavailable. Therefore, we conducted structured interviews of adults living in 5 towns in the remote Amazon region of Peru. Respondents (n = 179) were 67% women with a mean age of 35.4 years. The average household size was 6.7 people. A majority (72%) were unable to see a doctor when needed because of lack of money and distance. Only 6% reported excellent health, and nearly half (49%) reported fair health. Forty-eight percent drank alcohol and 73% smoked. Only 34% thought mosquitoes cause malaria, but 98% were using mosquito nets. In conclusion, our findings indicate the indigenous population of the Peruvian Amazon has limited access to basic health care. Although most of those surveyed use mosquito netting, few know that mosquitoes transmit malaria. Tobacco and alcohol use are major behavioral health risk factors.

Journal of Tropical Pediatrics 2001, 47/4 (230-238)

Treatment of childhood fevers and other illnesses in three rural Nigerian communities

Salako L.A.; Brieger W.R.; Afolabi B.M.; Umeh R.E.; Agomo P.U.; Asa S.; Adeneye A.K.; Nwankwo B.O.; Akinlade C.O.

W.R. Brieger, African Regional Hlth. Educ. Center, College of Medicine, University of Ibadan, Ibadan Nigeria

The seeking of healthcare for childhood illnesses was studied in three rural Nigerian communities of approximately 10 000 population each. The aim was to provide a baseline understanding of illness behaviour on which to build a programme for the promotion of prepackaged chloroquine and cotrimoxazole for early and appropriate treatment of childhood fevers at the community level. A total of 3117 parents of children who had been ill during the 2 weeks prior to interview responded to questions about the nature of the illness and the actions taken. Local illness terms were elicited, and the most prevalent recent illness and the actions taken.

Local illness terms were elicited, and the most prevalent recent illnesses were 'hot body' (43.9 per cent), malaria, known as iba (17.7 per cent), and cough (7.4 per cent). The most common form of first-line treatment was drugs from a patent medicine vendor or drug hawker (49.6 per cent). Only 3.6 per cent did nothing. Most who sought care (77.5 per cent) were satisfied with their first line of action, and did not seek further treatment. The average cost of an illness episode was less than US$2.00 with a median of US$1.00. Specifically, chloroquine tablets cost an average of US 29cents per course. Analysis found a configuration of signs and symptoms associated with chloroquine use, to include perception of the child having malaria, high temperature and loss of appetite. The  configuration positively associated with antibiotic use consisted of cough and difficult breathing. The ability of the child's care-givers, both parental and professional, to make these distinctions in medication use will provide the foundation for health education in the promotion of appropriate early treatment of childhood fevers in the three study sites.


Clinical Infectious Diseases SEP 2001, 33/5 (651-661)

Malaria on the world wide web

Angus B.J.
Dr. B.J. Angus, Dept. of Tropical Medicine, Nuffield Dept. of Medicine,
John Radcliffe Hospital, Headington, Oxford 0X3 9DU United Kingdom
Email: [email protected]

The Internet is enabling scientists and clinicians in areas with endemic malaria to transfer information to scientists and clinicians in other countries. This should allow changes in therapy to follow the rapid changes in the disease that have posed such difficulties in the past. This article reviews Internet resources that focus on malaria. This includes 90 Web sites in 12 sections. Authoritative multinational organizational sites and regional sites, such as those in Africa, Asia (including Thailand and India), and South America (in Venezuela and Brazil), are described. Basic research-oriented databases, such as those that deal with plasmodia genomics, biochemistry, and vaccine development, as well as vector information and geographic satellite information systems, are reviewed. There is a section about malaria research-funding organizations that offer online applications. Useful teaching resources and journals, including those with full online access, are detailed.


PubMed

J Immunol 2001 Oct 1;167(7):3903-3909

Apoptotic Deletion of Th Cells Specific for the 19-kDa Carboxyl-Terminal Fragment of Merozoite Surface Protein 1 During Malaria Infection.

Wipasa J, Xu H, Stowers A, Good MF.

Cooperative Research Center for Vaccine Technology, Queensland Institute of Medical Research, Royal Brisbane Hospital, Queensland, Australia. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.

Immunity induced by the 19-kDa fragment of merozoite surface protein 1 is dependent on CD4(+) Th cells. However, we found that adoptively transferred CFSE-labeled Th cells specific for an epitope on Plasmodium yoelii 19-kDa fragment of merozoite surface protein 1 (peptide (p)24), but not OVA-specific T cells, were deleted as a result of P. yoelii infection. As a result of infection, spleen cells recovered from infected p24-specific T cell-transfused mice demonstrated reduced response to specific Ag. A higher percentage of CFSE-labeled p24-specific T cells stained positive with annexin and anti-active caspase-3 in infected compared with uninfected mice, suggesting that apoptosis contributed to deletion of p24-specific T cells during infection. Apoptosis correlated with increased percentages of p24-specific T cells that stained positive for Fas from infected mice, suggesting that P. yoelii-induced apoptosis is, at least in part, mediated by Fas. However, bystander cells of other specificities also showed increased Fas expression during infection, suggesting that Fas expression alone is not sufficient for apoptosis. These data have implications for the development of immunity in the face of endemic parasite exposure.

PMID: 11564808 [PubMed - as supplied by publisher]


Rev Soc Bras Med Trop 2001 Jul-Aug;34(4):343-348
Assessment of the response to reduced treatment schemes for vivax malaria

Abdon NP, Pinto AY, Silva Rd R, Souza JM.

Nucleo de Medicina Tropical, Universidade Federal do Para, Belem, PA.

Relapses may occur with long standard treatment of vivax malaria, and these are caused by incomplete patient's compliance. The use of reduced schedules may further better patient compliance, while maintaining the same efficacy, tolerance and minimal adverse reactions. The objective of this study was to test two schedules with reduced doses of chloroquine for vivax malaria and comparing these with the classical schedule. The authors studied 120 outpatients, with vivax malaria, aged over 12 years, submitted to three therapeutic schemes: scheme I: chloroquine phosphate (150mg) in a dose of 25mg/kg/day for three days (10mg/kg/ day in the first day, 7.5mg/kg/day in the second and third day), plus primaquine (15mg) in a dose of 0.25mg/kg/day for fourteen days; scheme II: chloroquine, in a single dose of 10mg/kg, plus primaquine in a dose of 0.5mg/kg/day for seven days; scheme III: chloroquine, 10mg/kg in a single dose plus primaquine in a dose 0.5mg/kg/ day for five days. The clinical response to all three therapeutic schemes was satisfactory. The disappearance of malarial symptoms occurred after a maximum 96 hours of treatment, while the assexual parasitaemia clearance occurred within 72 hours, in all therapeutic schemes.

PMID: 11562727 [PubMed - as supplied by publisher]

J Struct Biol 2001 Jul;135(1):47-57
 
Cryofracture Electron Microscopy of the Ookinete Pellicle of Plasmodium gallinaceum Reveals the Existence of Novel Pores in the Alveolar Membranes.

Raibaud A, Lupetti P, Paul RE, Mercati D, Brey PT, Sinden RE, Heuser JE, Dallai R.

Unite de Biochimie et Biologie Moleculaire des Insectes, Institut Pasteur, 25 rue du Docteur Roux, Paris Cedex 15, 75724, France

The malaria parasite invades the midgut tissue of its mosquito host as a motile form called the ookinete. We have examined the pellicle of the ookinete of Plasmodium gallinaceum by freeze-fracture and quick-freeze, deep-etch electron microscopy. The general organization is analogous to that of invasive stages of other members of Apicomplexa. The pellicle is composed of three membranes: the plasma membrane, and the two linked intermediate and inner membranes, which in the ookinete form one flattened vacuole that is located beneath the plasma membrane. The edges of this vacuole form a longitudinal suture. Beneath the vacuole is found an array of microtubules that are connected to the inner membrane by intramembranous particles. During freeze-fracture, the membranes can split along their hydrophobicplanes, thus yielding six fracture faces, each of which displays a characteristic pattern of intramembranous particles. Additionally, we find that the ookinete pellicle differs from all otherapicomplexan motile stages by the presenceof large pores. These pores are of unknown function, but clearly might constitute a novel pathway for the transport of molecules to and from the cortex, which is independent of the well-describedroute through the apical micronemal/rhoptry complex. The pores may be the routeby which motor proteins or other nonmicronemal surface proteins are trafficked, such as P25/P28 and SOAP, some of which are implicated in transmission blocking immunity. Copyright 2001 Academic Press.

PMID: 11562165 [PubMed - in process]


Am J Trop Med Hyg 2001 Sep;65(3):214-8
Prevention of sporogony of Plasmodium vivax in Anopheles dirus mosquitoes by transmission-blocking antimalarials.

Coleman RE, Polsa N, Eikarat N, Kollars TM Jr, Sattabongkot J.

Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

The sporontocidal activity of four dihydroacridine-diones (WR-233602, WR-243251, WR-250547, and WR-250548) and three fluoroquinolones (WR-279135, WR-279298, and WR-279288) was determined against naturally circulating isolates of Plasmodium vivax. Laboratory-reared Anopheles dirus mosquitoes were infected with P. vivax by feeding them on gametocytemic volunteers reporting to local malaria clinics in Kanchanaburi and Tak provinces, Thailand. Four days after the infectious feed, mosquitoes were re-fed on uninfected mice treated 90 minutes previously with a given drug at a dose of 100 mg base drug/kg mouse body weight. Sporontocidal activity was determined by assessing both oocyst and sporozoite development. None of the fluoroquinolones exhibited sporontocidal activity against P. vivax, whereas all 4 dihydroacridine-diones affected sporogonic development to some degree. WR-233602 affected oocyst development, but had no impact on sporozoite production, WR-250548 affected oocyst development and had a limited effect on sporozoite production, and WR-243251 and WR-250547 had a marked impact on all phases of sporogony. These data demonstrate that experimental dihydroacridine-diones are capable of interrupting the sporogonic development of P. vivax. These compounds may be useful in preventing malaria transmission.

PMID: 11561707 [PubMed - in process]


Am J Trop Med Hyg 2001 Sep;65(3):197-203
Incidence of symptomatic and asymptomatic Plasmodium falciparum infection following curative therapy in adult residents of northern Ghana.

Sowusu-Agyei S, Koram KA, Baird JK, Utz GC, Binka FN, Nkrumah FK, Fryauff DJ, Hoffman SL.

Navrongo Health Research Center, Ghana.

Adult residents of holoendemic malaria regions in Africa have a naturally acquired immunity (NAI) to malaria that renders them more resistant to new infections, limits parasitemia, and reduces the frequency and severity of illness. Given such attributes, it is not clear how one might evaluate drug or vaccine efficacy in adults without serious confounding. To determine symptomatic and asymptomatic malaria attack rates in adults of northern Ghana, 197 men and women underwent curative therapy for any pre-existing malaria infections at the start of the high transmission (wet) season. They were monitored for first parasitemia and first clinical episode of infection by Plasmodium falciparum over a 20-week period (May-October 1996). The cumulative incidence of primary infection by P. falciparum was 0.98 and incidence density of infection was calculated to be 7.0 cases/person-year. Symptoms were reported by 19.5% of the individuals at the time of first recurrent parasitemia. Incidence of infection, parasite density, and the frequency of symptoms were comparable in males and females. The results suggest that NAI did not provide these adults with significant defense against rapid re-infection and suggest that this population-infection design could serve to demonstrate the efficacy of a drug or vaccine in preventing parasitemia.

PMID: 11561704 [PubMed - in process]


Am J Trop Med Hyg 2001 Sep;65(3):167-70
Rapid reappearance of Plasmodium falciparum after drug treatment among Senegalese adults exposed to moderate seasonal transmission.

Sokhna CS, Faye FBK, Spiegel A, Dieng H, Trape JF.

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

To investigate the relationship between the entomologic inoculation rate (EIR) and time to reappearance of malaria parasites after radical treatment under moderate seasonal transmission conditions, a study was undertaken in a mesoendemic area of Senegal where malaria transmission is concentrated over an annual three-month period and averages 12 infective bites per person per year. A three-day course of quinine was administered to 48 asymptomatic adults between 19 and 66 years of age. Malaria transmission and parasitemia were monitored every week for two months and cases of fever or symptoms were investigated as part of a daily clinical surveillance. The proportion of persons reinfected at Days 28, 35, and 56 was 25%, 38%, and 54%, respectively. Adults less than 40 years of age had a shorter time to reinfection. In this age group, the median Plasmodium falciparum reappearance time was 28 days, and it was estimated that only one infected mosquito bite was able to induce a patent infection among half of the subjects. Only 8% (2 of 26) of the reinfections caused a clinical attack. These data are discussed in the light of previous studies conducted among adults naturally exposed to intense perennial transmission or among naive volunteers receiving artificial challenges. Rapid reinfection occurs at very low EIRs and dramatic differences in actual and cumulated exposure to infected mosquito bites poorly affect the median time to reappearance of malaria parasites in endemic populations.

PMID: 11561697 [PubMed - in process]


Biochemistry 2001 Sep 25;40(38):11518-11524
Direct Measurement of the Interactions of Glycosaminoglycans and a Heparin Decasaccharide with the Malaria Circumsporozoite Protein.

Rathore D, McCutchan TF, Garboczi DN, Toida T, Hernaiz MJ, LeBrun LA, Lang SC, Linhardt RJ.

Growth and Development Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, Structural Biology Section, Laboratory of Immunogenetics, NIAID, NIH, Rockville, Maryland 20852, Department of Analytical Chemistry, School of Pharmacy, Chiba University, Chiba, Japan, and Departments of Medicinal and Natural Products Chemistry, Chemistry, Chemical and Biochemical Engineering, University of Iowa, Iowa City, Iowa 52242.

Circumsporozoite (CS) protein is a predominant surface antigen of malaria sporozoites, the infective form of the parasite, and has been used for making anti-malaria vaccines. For the first time we have examined the interaction of CS protein with various glycosaminoglycans in real time using surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Heparin was the best binder among the glycosaminoglycans tested and bound to CS protein with nanomolar affinity. Using purified and structurally defined small heparin oligosaccharides, we identified a decasaccharide to be the minimum sized CS protein-binding sequence. In an indirect competition assay, this decasaccharide blocked the CS protein interaction with HepG2 cells with an ID(50) of less than 60 nM. The decasaccharide has a structure commonly found in hepatic heparan sulfate, and the same sequence has recently been shown to bind specifically to apolipoprotein E. Examination of porcine liver heparan sulfate in this indirect competition assay showed that it and heparin were the only glycosaminoglycans that could effectively block CS protein interaction with HepG2 cells in culture. These data support the hypothesis that the invasion of liver cells by the parasite shares a common mechanism with the hepatic uptake of lipoprotein remnants from the blood.

PMID: 11560500 [PubMed - as supplied by publisher]


Eur J Biochem 2001 Sep;268(18):4842-4849
The H89 cAMP-dependent protein kinase inhibitor blocks Plasmodium falciparum development in infected erythrocytes.

Syin C, Parzy D, Traincard F, Boccaccio I, Joshi MB, Lin DT, Yang XM, Assemat K, Doerig C, Langsley G.

Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD, USA; Institut de Medecine Tropical du Service de Sante des Armees, Le Pharo, Marseille, France; Unite de Regulation Enzymatique des Activites Cellulaires, FRE CNRS 2364, Departement de Biologie Moleculaire, Institut Pasteur, Paris, France; INSERM U399, Marseille, France; Unite de Biochimie Structurale, Departement d'Immunologie, Institut Pasteur, Paris, France; INSERM U 511, La Pitie-Salpetriere, Paris, France; Laboratoire de Signalization Immunoparasitaire, URA CNRS 1960, Departement d'Immunologie, Institut Pasteur, Paris, France.

In Plasmodium falciparum, the causative agent of human malaria, the catalytic subunit gene of cAMP-dependent protein kinase (Pfpka-c) exists as a single copy. Interestingly, its expression appears developmentally regulated, being at higher levels in the pathogenic asexualstages than in the sexual forms of parasite that areresponsible for transmission to the mosquito vector. Within asexual parasites, PfPKA activity can be readily detected in schizonts. Similar to endogenous PKA activityofnoninfected red blood cells, the parasite enzymecan be stimulated by cAMP and inhibited by protein kinase inhibitor.Importantly, exvivo treatment of infected erythrocytes with the classical PKA-C inhibitor H89 leads to a block in parasite growth. This suggests that the PKA activities of infected red blood cells are essential for parasite multiplication. Finally, structural considerations suggest that drugs targeting the parasite, rather than the erythrocyte enzyme, might be developed that could help in the fight against malaria.

PMID: 11559352 [PubMed - as supplied by publisher]

Rev Inst Med Trop Sao Paulo 2001 Jul-Aug;43(4):221-6
 
In vitro evaluation of quinidine sensitivity in brazilian Plasmodium falciparum isolates: comparative analysis to quinine and chloroquine.

Menezes CM, Kirchgatter K, Di Santi SM, A Paula G, Ferreira EI.

Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, Sao Paulo, SP, Brasil.

Falciparum malaria represents a serious and an increasing world public health problem due to the acquired parasite's resistance to the most available drugs. In some endemic areas, quinidine, a diastereoisomer of the antimalarial quinine, has been employed for replacing the latter. In order to evaluate the use of quinidine as an alternative to the increasing loss of quinine effectiveness in Brazilian P. falciparum strains, as has been observed in the Amazon area, we have assayed quinidine, quinine and chloroquine. The in vitro microtechnique was employed. All isolates showed to be highly resistant to chloroquine. Resistance to quinine was not noted although high MIC (minimal inhibitory concentration) values have been observed. These data corroborate the decreasing sensitivity to quinine in strains from Brazil. Quinidine showed IC50 from 0.053 to 4.577 &mgr;mol/L of blood while IC50 from 0.053 to 8.132 &mgr;mol/L of blood was estimated for quinine. Moreover, clearance of the parasitemia was observed in concentrations lower than that used for quinidine in antiarrhythmic therapy, confirming our previous data. The results were similar to African isolate.

PMID: 11558003 [PubMed - in process]


Science 2001 Sep 14;293(5537):2098-100
Role of nonimmune IgG bound to PfEMP1 in placental malaria.

Flick K, Scholander C, Chen Q, Fernandez V, Pouvelle B, Gysin J, Wahlgren M.

Microbiology and Tumor Biology Center (MTC), Karolinska Institutet and Swedish Institute for Infectious Disease Control, Box 280, S-171 77 Stockholm, Sweden.

Infections with Plasmodium falciparum during pregnancy lead to the accumulation of parasitized red blood cells (infected erythrocytes, IEs) in the placenta. IEs of P. falciparum isolates that infect the human placenta were found to bind immunoglobulin G (IgG). A strain of P. falciparum cloned for IgG binding adhered massively to placental syncytiotrophoblasts in a pattern similar to that of natural infections. Adherence was inhibited by IgG-binding proteins, but not by glycosaminoglycans or enzymatic digestion of chondroitin sulfate A or hyaluronic acid. Normal, nonimmune IgG that is bound to a duffy binding-like domain beta of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) might at the IE surface act as a bridge to neonatal Fc receptors of the placenta.

PMID: 11557894 [PubMed - in process]


Southeast Asian J Trop Med Public Health 2001 Jun;32(2):282-9
The efficacy of different mosquito trapping methods in a forest-fringe village, Yunnan Province, Southern China.

Moore SJ, Zunwei D, Hongning Z, Xuezhong W, Hongbing L, Yujiang X, Hill N.

London School of Hygiene and Tropical Medicine, UK.

Despite a control program, malaria incidence in Yunnan has increased and knowledge of vector bionomics is needed for efficient control. Multi-drug resistant Plasmodium falciparum necessitates alternatives to human landing catches as a means of studying vectors. Therefore CDC light traps with UV or ordinary incandescent bulbs were tested for 57 trap nights. 2,703 mosquitos were caught, including the vector species An. minimus and An. sinensis and the suspected vector An. maculatus. Larval An. dirus were found around the village but no adults were trapped. UV light traps caught more mosquitos than the traps with incandescent bulbs, but caught many insects other than mosquitos requiring time-consuming separation, and were unpopular with villagers. Traps placed in living areas of houses caught more mosquitos than those placed beside bednets and the catch mainly comprised species that were active in the early evening. Encephalitis Vector Surveillance (EVS) traps hung outdoors and baited with CO2 caught few mosquitos. CDC traps in the same position baited with CO2 or lactic acid caught large numbers of Culex tritaeniorhynchus. Indoor spray catches recovered human fed An. vagus and An. minimus. This work confirmed that CDC light traps could be used to trap local vectors, and the abundance of early active mosquitos in the living area suggests that personal protection measures may be required in the evening, to supplement bed net use.

PMID: 11556577 [PubMed - in process]


Southeast Asian J Trop Med Public Health 2001 Jun;32(2):275-81
Possibility of false-positive detection for sporozoites in mosquitos (Diptera: Culicidae) by nested polymerase chain reaction using Plasmodium yoelii genomic DNA.

Tsuzuki A, Toma T, Miyagi I, Toma H, Arakawa T, Sato Y, Kobayashi J, Mugissa MF.

Laboratory of Medical Zoology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.

Anopheles stephensi Liston and An. saperoi Bohart and Ingram infected with the rodent malaria parasite Plasmodium yoelii nigeriense. They were examined 12 and 19 days after blood feeding for sporozoites in head with anterior thorax (HT) and oocysts in abdomen with posterior thorax (AB) by light microscopy and by the nested polymerase chain reaction (nested PCR-based on the amplification of the sequences of the small subunit ribosomal RNA gene). The detection rate of parasite DNA by nested PCR in HT samples 12 days after blood feeding was similar to that by microscopic method. However, in HT samples 19 days after blood feeding, the rate by the PCR method was higher than that by the microscopic method. The incidence of sporozoites in salivary glands of infected mosquitos for 12 days after blood sucking was examined by the PCR method. Parasite DNA in HT of Aedes albopictus Skuse (a non vector for the rodent malaria) as well as An. stephensi and An. saperoi was detected for up to 4 days after feeding on mouse with the rodent malaria parasites. The results indicate that when the PCR method is used for detection of sporozoites of human malaria in mosquitos collected in the field, there are possibilities of including false-positive data for mosquitos that have just or recently fed on human blood infected with malaria (erythrocytic form).

PMID: 11556576 [PubMed - in process]


Southeast Asian J Trop Med Public Health 2001 Jun;32(2):268-74
Lack of association between CSF nitrate and sera nitrate in falciparum malaria infection.

Maneerat Y, Wilairatana P, Udomsangpetch R, Looareesuwan S.

Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University.

Nitrate levels in CSF and sera from 16 coma and 19 noncoma falciparum malaria patients were determined using nitric oxide colorometric assay. The medians (range lower, upper limits) of nitrate in sera of comatose and noncomatose patients were 0.28 (0.11, 1.24) and 0.23 (0.05, 0.87) microM, respectively. The medians of nitrate level in CSF of coma and noncoma cases were 0.09 (0.01, 0.28) and 0.15 (0, 1.18) microM, respectively. There was no difference of nitrate level in sera and CSF from comatose or noncomatose patients compared to that in normal sera and CSF. The amount of nitrate in sera and CSF of both groups was not significantly correlated with coma depth, parasitemia, parasite clearance time and time to recovery. Contrast to our in vitro study using immunoperoxidase staining, we found inducible nitric oside synthase production by brain endothelial cells during 4-24 hours of coculturing with late stage of P. falciparum infected red blood cells. These results suggests that malaria severity can not be differentiated by nitrate level in body fluid.

PMID: 11556575 [PubMed - in process]


Southeast Asian J Trop Med Public Health 2001 Jun;32(2):262-7
The relationship between anthropometric indicators of nutritional status and malaria infection among youths in Khammouane Province, Lao PDR.

Takakura M, Uza M, Sasaki Y, Nagahama N, Phommpida S, Bounyadeth S, Kobayashi J, Toma T, Miyagi I.

Department of School Health, School of Health Sciences, University of the Ryukyus, Nishihara, Okinawa, Japan. Email: [email protected]

We assessed anthropometric indicators of the nutritional status among children and adolescents in Khammouane Province in the Lao PDR and examined the relation between malnutrition and malaria infection. The survey was conducted from July to August 1999 using a sample of 309 youths aged 2 to 18 years. Malnutrition was categorized as stunting (below -2 Z scores height-for-age) and wasting (below -2 Z scores weight-for-height). The prevalence of stunting and wasting were 45.1% and 9.2%, respectively, which were classified by WHO as "very high" prevalence. Compared with the results of previous national surveys in Lao PDR, similar prevalence was shown. The prevalence of wasting in youths with P. falciparum infection was 17%, significantly higher than those of not infected (4%). On the other hand, P. vivax infection was not associated with any indicators of malnutrition. In conclusion, this study showed that the nutritional status in youths was poor and P. falciparum infection was associated with acute malnutrition.

PMID: 11556574 [PubMed - in process]


Southeast Asian J Trop Med Public Health 2001 Jun;32(2):255-61
Clinical trial of halofantrine with modified doses for treatment of malaria in the hospital for tropical diseases.

Krudsood S, Singhasivanon P, Silachamroon U, Treeprasertsuk S, Kaivipakbanyai W, Chalermrut K, Phophak N, Horton J, Kyle D, Looareesuwan S.

Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

The spread of falciparum malaria resistant to chloroquine all over Southeast Asian continent has led to increasing use of alternative antimalarial drugs. Halofantrine has been shown to be effective against multidrug resistant Plasmodium falciparum. One hundred and twenty falciparum malaria cases were randomly assigned to one of three different halofantrine regimes. Group I (HA1) received 500 mg three times daily for 3 days (total dose: 4,500 mg), group II (HA2) received 500 mg three times daily for the first and the third day (total dose: 3,000 mg) and group III (HA3) received 500 mg three times for one day followed by 500 mg once daily for 7 days (total dose: 4,500 mg). No significant difference in the cure rate was observed among the three regimes (cure rate: 89%, 73%, 97% respectively). However, the cure rate was significantly higher in the HA3 group when compared to the HA2 group. There were no overt cardiac problems seen in this study. Thus, halofantrine has high efficacy in the recommended treatment dose of 500 mg three times after meals on the first day followed by 500 mg once a day after a meal for 7 days (total dose: 4,500 mg).

PMID: 11556573 [PubMed - in process]


Southeast Asian J Trop Med Public Health 2001 Jun;32(2):247-54
Natural human IgG subclass antibodies to Plasmodium falciparum blood stage antigens and their relation to malaria resistance in an endemic area of Thailand.

Tangteerawatana P, Krudsood S, Chalermrut K, Looareesuwan S, Khusmith S.

Department of Microbiology, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand.

The immunoglobulin G (IgG) subclass antibodies to Plasmodium falciparum blood stage antigens in the sera of 181 individuals living in malaria endemic area in Kanchanaburi Province, western Thailand, were determined by enzyme-linked immunosorbent assay (ELISA). In this study, IgG3 and IgG1 were shown to be the predominant subclasses. Generally, IgG2 were coexpressed with IgG1 and IgG3 while IgG4 was found to coexpress with other three IgG subclasses. The levels of specific IgG1, IgG2, and IgG3 increased significantly with age (r = 0.295, p = 0.000; r = 0.416, p = 0.000; r = 0.320, p = 0.000, respectively). The data indicate that the higher antibody production required continuous stimulation under natural condition. Furthermore, the levels of specific IgG1, IgG2 and IgG3 increased in immune individuals without clinical malaria, reported in adolescents and adults, were associated with malaria resistance. Similar results were found in children with different patterns of IgG subclasses in which the specific IgG2 and IgG3, but not IgG1 was related to resistance.

PMID: 11556572 [PubMed - in process]


Trop Med Int Health 2001 Aug;6(8):607-13
Genetic diversity of Plasmodium falciparum and its relationship to parasite density in an area with different malaria endemicities in West Uganda.

Peyerl-Hoffmann G, Jelinek T, Kilian A, Kabagambe G, Metzger WG, von Sonnenburg F.

Department of Infectious Diseases and Tropical Medicine, University of Munich, Germany; Basic Health Services, GTZ, Fort Portal, Uganda; District Health Services, Kabarole District, Uganda.

Field populations of Plasmodium falciparum can be effectively genotyped by PCR-amplification of selected fragments of the Merozoite Surface Proteins 1 and 2 (MSP1 and MSP2). Genetic diversity of P. falciparum populations in areas with different transmission levels (holo- vs. mesoendemic) was investigated in Kabarole District, West Uganda. 225 samples positive for P. falciparum were analysed by amplification of polymorphic regions and classified according to prevalence of allelic families. A large number of alleles was detected for each locus: 22 for MSP1 block 2 and 24 for MSP2 and, 175 (78%) of MSP1 alleles and 143 (64%) of MSP2 showed multiple infections within a range of 2-8 clones. Significant differences between holoendemic and mesoendemic areas in regards of population structure and number of multiclonal infections of P. falciparum were not apparent. However, a significant correlation between parasite density, selected MSP2 loci and differences between parasite density in monoclonal vs. multiclonal infections occurred. Multiplicity of infection was age-dependent.

PMID: 11555426 [PubMed - in process]

Proc Natl Acad Sci U S A 2001 Sep 11;98(19):10769-74
When genetic distance matters: measuring genetic differentiation at microsatellite loci in whole-genome scans of recent and incipient mosquito species.

Wang R, Zheng L, Toure YT, Dandekar T, Kafatos FC.

European Molecular Biology Laboratory, Meyerhofstrasse 1, 69012 Heidelberg, Germany.

Genetic distance measurements are an important tool to differentiate field populations of disease vectors such as the mosquito vectors of malaria. Here, we have measured the genetic differentiation between Anopheles arabiensis and Anopheles gambiae, as well as between proposed emerging species of the latter taxon, in whole genome scans by using 23-25 microsatellite loci. In doing so, we have reviewed and evaluated the advantages and disadvantages of standard parameters of genetic distance, F(ST), R(ST), (delta mu)(2), and D. Further, we have introduced new parameters, D' and D(K), which have well defined statistical significance tests and complement the standard parameters to advantage. D' is a modification of D, whereas D(K) is a measure of covariance based on Pearson's correlation coefficient. We find that A. gambiae and A. arabiensis are closely related at most autosomal loci but appear to be distantly related on the basis of X-linked chromosomal loci within the chromosomal Xag inversion. The M and S molecular forms of A. gambiae are practically indistinguishable but differ significantly at two microsatellite loci from the proximal region of the X, outside the Xag inversion. At one of these loci, both M and S molecular forms differ significantly from A. arabiensis, but remarkably, at the other locus, A. arabiensis is indistinguishable from the M molecular form of A. gambiae. These data support the recent proposal of genetically differentiated M and S molecular forms of A. gambiae.

PMID: 11553812 [PubMed - in process]


Proc Natl Acad Sci U S A 2001 Sep 11; [epub ahead of print]
Complete, long-lasting protection against malaria of mice primed and boosted with two distinct viral vectors expressing the same plasmodial antigen.

Bruna-Romero O, Gonzalez-Aseguinolaza G, Hafalla JC, Tsuji M, Nussenzweig RS.

Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010.

We report that complete protection against malaria and total inhibition of liver stage development and parasitemia was obtained in 100% of BALB/c mice primed with a replication-defective recombinant adenovirus expressing the circumsporozoite (CS) protein of Plasmodium yoelii (AdPyCS), followed by a booster with an attenuated recombinant vaccinia virus, expressing the same malaria antigen, VacPyCS. We found increased levels of activated CS-specific CD8(+) and CD4(+) T cells, higher anti-sporozoite antibody titers, and greater protection in these mice, when the time between priming and boosting with these two viral vectors was extended from 2 to 8 or more weeks. Most importantly, by using this immunization regimen, the protection of the immunized mice was found to be long-lasting, namely complete resistance to infection of all animals 3 1/2 months after priming. These results indicate that immunization with AdPyCS generates highly effective memory T and B cells that can be recalled long after priming by boosting with VacPyCS.

PMID: 11553779 [PubMed - as supplied by publisher]


Mol Biochem Parasitol 2001 Sep;117(1):83-9
The 22 kDa component of the protein complex on the surface of Plasmodium falciparum merozoites is derived from a larger precursor, merozoite surface protein 7.

Pachebat JA, Ling IT, Grainger M, Trucco C, Howell S, Fernandez-Reyes D, Gunaratne R, Holder AA.

Division of Parasitology, National Institute for Medical Research, Mill Hill, NW7 1AA, London, UK

The gene coding for merozoite surface protein 7 has been identified and sequenced in three lines of Plasmodium falciparum. The gene encodes a 351 amino acid polypeptide that is the precursor of a 22-kDa protein (MSP7(22)) on the merozoite surface and non-covalently associated with merozoite surface protein 1 (MSP1) complex shed from the surface at erythrocyte invasion. A second 19-kDa component of the complex (MSP7(19)) was shown to be derived from MSP7(22) and the complete primary structure of this polypeptide was confirmed by mass spectrometry. The protein sequence contains several predicted helical and two beta elements, but has no similarity with sequences outside the Plasmodium databases. Four sites of sequence variation were identified in MSP7, all within the MSP7(22) region. The MSP7 gene is expressed in mature schizonts, at the same time as other merozoite surface protein genes. It is proposed that MSP7(22) is the result of cleavage by a protease that may also cleave MSP1 and MSP6. A related gene was identified and cloned from the rodent malaria parasite, Plasmodium yoelii YM; at the amino acid level this sequence was 23% identical and 50% similar to that of P. falciparum MSP7.

PMID: 11551634 [PubMed - in process]


Mol Biochem Parasitol 2001 Sep;117(1):49-59
Erythrocyte-binding activity of Plasmodium yoelii apical membrane antigen-1 expressed on the surface of transfected COS-7 cells.

Fraser TS, Kappe SH, Narum DL, VanBuskirk KM, Adams JH.

Department of Biological Sciences, University of Notre Dame, 46556-0369, Notre Dame, IN, USA

Malaria merozoite surface and apical organellar molecules facilitate invasion into the host erythrocyte. The underlying molecular mechanisms of invasion are poorly understood, and there are few data to delineate roles for individual merozoite proteins. Apical membrane antigen-1 (AMA-1) is a conserved apicomplexan protein present in the apical organelle complex and at times on the surface of Plasmodium and Toxoplasma zoites. AMA-1 domains 1/2 are conserved between Plasmodium and Toxoplasma and have similarity to the defined ligand domains of MAEBL, an erythrocyte-binding protein identified from Plasmodium yoelii. We expressed selected portions of the AMA-1 extracellular domain on the surface of COS-7 cells to assay for erythrocyte-binding activity. The P. yoelii AMA-1 domains 1/2 mediated adhesion to mouse and rat erythrocytes, but not to human erythrocytes. Adhesion to rodent erythrocytes was sensitive to trypsin and chymotrypsin, but not to neuraminidase. Other parts of the AMA-1 ectodomain, including the full-length extracellular domain, mediated significantly less erythrocyte adhesion activity than the contiguous domains 1/2. The results support the role of AMA-1 as an adhesion molecule during merozoite invasion of erythrocytes and identify highly conserved domains 1/2 as the principal ligand of the Plasmodium AMA-1 and possibly the Toxoplasma AMA-1. Identification of the AMA-1 ligand domains involved in interaction between the parasite and host cell should help target the development of new therapies to block growth of the blood-stage malaria parasites.

PMID: 11551631 [PubMed - in process]

Mol Biochem Parasitol 2001 Sep;117(1):1-10
The 235 kDa rhoptry protein of Plasmodium (yoelii) yoelii: function at the junction.

Khan SM, Jarra W, Preiser PR.

Division of Parasitology, The National Institute for Medical Research, The Ridgeway, Mill Hill, NW7 1AA, London, UK

All malaria parasites are obligate intracellular organisms that must clearly recognise and discriminate between different cells during their life cycle. Invasion into a cell is a multi-step event that is marked by initial attachment proceeding to irreversible junction formation and penetration. A 235 kDa rhoptry protein (Py235) in the rodent malaria, Plasmodium yoelii yoelii has been shown to be involved in red blood cell (rbc) binding and is involved in a new mechanism of clonal phenotypic variation that may be important in adaptation and immune evasion. Immunisation studies using Py235 have also revealed a role for this protein in the virulence phenotype seen with P. y. yoelii in laboratory mice. Interestingly, the genes that encode this protein are present as a multi-gene family. In this paper, we examine Py235 at the level of DNA, transcription and expression, discussing the role of this protein during invasion, in virulence and in immune evasion.

PMID: 11551627 [PubMed - in process]

Microbios 2001;106 Suppl 2:117-32

An analysis of haematological parameters in patients and individual residents of a Plasmodium falciparum malaria holoendemic area of western Kenya.

Orago AS, Wattimah DN, Aloka PL, Gitau CW, Orago MA, Onyango TG.

Department of Zoology, Kenyatta University, Nairobi, Kenya.

Many clinical symptoms of malaria are associated with alterations in certain haematological parameters during acute and subclinical infections. Total leucocyte and erythrocyte counts, haemoglobin concentration, haematocrit and other minor indices, were investigated in five cohort groups of individuals resident in a malaria hyperendemic area of western Kenya. The groups included age- and sex-matched adults with acute Plasmodium falciparum malaria, aparasitaemic adults, children with acute malaria, aparasitaemic children and asymptomatic-parasitaemic school children. The study aimed at defining what constitutes immunity to malaria which may be important in the critical evaluation of malaria vaccine antigens. Anaemia was more severe in adults and children with acute malaria than in their age- and sex-matched aparasitaemic and asymptomatic-aparasitaemic school children. Lymphocyte counts were significantly higher in asymptomatic-aparasitaemic school children than in aparasitaemic adults, suggesting a possible functional role for lymphocytes in the anti-disease immunity in the former group.

PMID: 11548200 [PubMed - in process]

S Afr Med J 2001 Jul;91(7):592-4

Effectiveness of short-course quinine and single-dose sulfadoxine-pyrimethamine in the treatment of Plasmodium falciparum malaria in Mpumalanga Province, South Africa.

Athan E, Durrheim DN, Barnes K, Mngomezulu NM, Mabuza A, Govere J.

Infectious Diseases Service, Geelong, Australia.

INTRODUCTION: Quinine therapy for 7 days remains the mainstay for treating hospitalised malaria cases in South Africa. However, limited resources, including available beds and staff, often result in early discharge of non-severe cases, with quinine tablets for outpatient use. The effectiveness of shorter course quinine therapy coupled with a long-acting antimalarial drug has never been established in Africa, in particular in a population without malaria immunity. METHODS: A study was conducted to evaluate the effectiveness of a 3-day course of therapy with quinine sulphate (10 mg/kg 8-hourly) followed by a single dose of sulfadoxine-pyrimethamine (SP) according to weight category, before discharge, for 133 hospitalised patients with uncomplicated Plasmodium falciparum malaria at Shongwe Hospital, Mpumalanga province, between February and July 1998. Study endpoints included clinical recovery and parasitological cure, including polymerase chain reaction (PCR) 42 days after initiating treatment. RESULTS: One hundred and thirty of 131 patients (99%) successfully followed up for 42 days demonstrated clinical and parasitological cure. The remaining patient, who had evidence of a recrudescent infection on PCR, was 1 of 61 patients who were still parasitaemic on discharge from hospital. CONCLUSION: The abbreviated course of quinine therapy coupled with a single dose of SP for the treatment of non-severe hospitalised cases of P. falciparum malaria, in an area with demonstrated low levels of SP resistance, was highly effective. This approach has potential benefits, including reduced duration of hospitalisation, fewer quinine-associated adverse events and protection against the evolution of quinine resistance by limiting unsupervised quinine therapy in the community. It may, however, be prudent to document a negative blood film before discharge from hospital.

PMID: 11544977 [PubMed - indexed for MEDLINE]


Jpn J Infect Dis 2001 Jun;54(3):114-6
Absence of association between the allele coding methionine at position 29 in the N-terminal domain of ICAM-1 (ICAM-1(Kilifi)) and severe malaria in the northwest of Thailand.

Ohashi J, Naka I, Patarapotikul J, Hananantachai H, Looareesuwan S, Tokunaga K.

Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan. Email: [email protected]

Intercellular adhesion molecule 1 (ICAM-1) is known to be the endothelial receptor for Plasmodium falciparum-infected erythrocytes. Associations of the variant allele coding methionine at position 29 in the N-terminal domain of ICAM-1, ICAM-1(Kilifi), with severe malaria have been investigated in African populations, and the results of these investigations have varied widely. In this study, we investigated a possible association between the ICAM-1(Kilifi) and severe malaria in adult malaria patients living in northwest Thailand. The frequencies of the ICAM-1(Kilifi) among patients with mild malaria, with non-cerebral severe malaria, and with cerebral malaria were 1.7%, 2.7%, and 2.3%, respectively. This variant showed neither positive nor negative association with severe malaria in Thailand.

PMID: 11544402 [PubMed - in process]


Annu Rev Microbiol 2001;55:673-707
Antigenic variation at the infected red cell surface in malaria.

Kyes S, Horrocks P, Newbold C.

Molecular Parasitology Group, Weatherall Institute of Molecular Medicine, Headington, Oxford OX3 9DS United Kingdom; 
Email: [email protected]
Email: [email protected]
Email: [email protected]

Many pathogens that either rely on an insect vector to complete their life cycle (e.g., Trypanosoma spp. and Borrelia spp.) or exist in a unique ecological niche where transmission from host to host is sporadic (e.g., Neisseria spp.) have evolved strategies to maintain infection of their mammalian hosts for long periods of time in order to ensure their survival. Because they have to survive in the face of a fully functional immune system, a common feature of many of these organisms is their development of sophisticated strategies for immune evasion. For the above organisms and for malaria parasites of the genus Plasmodium, a common theme is the ability to undergo clonal antigenic variation. In all cases, surface molecules that are important targets of the humoral immune response are encoded in the genome as multicopy, nonallelic gene families. Antigenic variation is accomplished by the successive expression of members of these gene families that show little or no immunological cross-reactivity. In the case of malaria parasites, however, some of the molecules that undergo antigenic variation are also major virulence factors, adding an additional level of complication to the host-parasite interaction. In this review, we cover the history of antigenic variation in malaria and then summarize the more recent data with particular emphasis on Plasmodium falciparum, the etiological agent of the most severe form of human malaria.

PMID: 11544371 [PubMed - in process]


J Med Chem 2001 Sep 13;44(19):3187-94
Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents.

Wright CW, Addae-Kyereme J, Breen AG, Brown JE, Cox MF, Croft SL, Gokcek Y, Kendrick H, Phillips RM, Pollet PL.

The School of Pharmacy and Cancer Research Unit, University of Bradford, West Yorkshire, BD7 1DP, U.K., and the Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, U.K.

The indoloquinoline alkaloid cryptolepine 1 has potent in vitro antiplasmodial activity, but it is also a DNA intercalator with cytotoxic properties. We have shown that the antiplasmodial mechanism of 1 is likely to be due, at least in part, to a chloroquine-like action that does not depend on intercalation into DNA. A number of substituted analogues of 1 have been prepared that have potent activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum and also have in common with chloroquine the inhibition of beta-hematin formation in a cell-free system. Several compounds also displayed activity against Plasmodium berghei in mice, the most potent being 2,7-dibromocryptolepine 8, which suppressed parasitemia by 89% as compared to untreated infected controls at a dose of 12.5 mg kg(-1) day(-1) ip. No correlation was observed between in vitro cytotoxicity and the effect of compounds on the melting point of DNA (DeltaT(m) value) or toxicity in the mouse-malaria model.

PMID: 11543688 [PubMed - in process]


Environ Entomol 1996 Oct;25(5):1058-67
Anopheles albimanus (Diptera: Culicidae) and cyanobacteria: an example of larval habitat selection.

Rejmankova E, Roberts DR, Manguin S, Pope KO, Komarek J, Post RA.

Division of Environmental Studies, University of California, Davis 95616, USA.

Northern Belize has extensive herbaceous wetlands. Those dominated by sparse emergent macrophytes, rushes (Eleocharis spp.) and sawgrass (Cladium jamaicense Crantz), often develop floating mats of cyanobacteria (blue-green algae). These mats provide suitable habitat for larvae of the malaria transmitting mosquito Anopheles albimanus Wiedemann. Presence/absence of A. albimanus larvae and cyanobacterial mats was assessed in marshes located throughout northern Belize. Of the 21 marshes examined during the 1993 wet and 1994 dry seasons, cyanobacterial mats were found in 11 and A. albimanus larvae were detected in 9 of these 11 marshes. No A. albimanus larvae were found in marshes without cyanobacterial mats. Mosquito larvae were collected along two 1,000 m long transects in both the wet season (August 1993) and the dry season (March 1994) to delineate larval distribution in marshes with cyanobacterial mats. A. albimanus larval densities in cyanobacterial mats were relatively high in both seasons: 2.8 and 2.3 larvae per dip in the wet and dry seasons, respectively, in Chan Chen marsh; and 0.8 and 1.02 larvae per dip in Buena Vista marsh. Numbers of larvae per dip did not significantly change with increasing distance from houses/pastures or margins of the marsh. A field experiment showed a strong preference of ovipositing A. albimanus for cyanobacterial mats. Higher temperatures and higher CO2 emissions from cyanobacterial mats are possible ovipositional cues.

PMID: 11540613 [PubMed - indexed for MEDLINE]


Ecol Appl 1994 Feb;4(1):81-90
Remote sensing of tropical wetlands for malaria control in Chiapas, Mexico.

Pope KO, Rejmankova E, Savage HM, Arredondo-Jimenez JI, Rodriguez MH, Roberts DR.

Geo Eco Arc Research, La Canada, California 91011, USA.

Malaria, transmitted by anopheline mosquitoes, remains a serious health problem in the tropics. Most malaria eradication efforts focus on control of anopheline vectors. These efforts include the NASA Di-Mod project, whose current goal is to integrate remote sensing, geographic information systems (GIS), and field research to predict anopheline mosquito population dynamics in the Pacific coastal plain of Chiapas, Mexico. Field studies demonstrate that high larval production of Anopheles albimanus, the principal malaria vector in the plain, can be linked to a small number of larval habitat-types, determined by larval sampling and cluster analysis of wetlands in the coastal plain. Analysis of wet and dry season Landsat Thematic Mapper (TM) satellite imagery identified 16 land cover units within an 185-km2 study area in the coastal zone. A hierarchical approach was used to link the larval habitat-types with the larger land cover units and make predictions of potential and actual low, medium, and high anopheline production. The TM-based map and GIS techniques were then used to predict differences in anopheline production at two villages, La Victoria and Efrain Gutierrez. La Victoria was predicted to have much higher Anopheles albimanus production, based upon a 2-10 times greater extent of medium- and high-producing land cover units in its vicinity. This difference between villages was independently supported by sampling (with light traps) of adults, which were 5-10 times more abundant in La Victoria.
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Last modified September 21, 2001