EHP Library Malaria Bulletin: April 20-27, 2001

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Social Sciences and Malaria

Effect of large-scale social marketing of insecticide-treated nets on child survival in rural Tanzania – Lancet 357(9264) April 21, 2001

(Full-text available via the Lancet web site at http://www.thelancet.com or send an email to [email protected] to request an electronic copy)

Joanna R M Armstrong Schellenberg, Salim Abdulla, Rose Nathan, Oscar Mukasa, Tanya J Marchant, Nassor Kikumbih, Adiel K Mushi, Haji Mponda, Happiness Minja, Hassan Mshinda, Marcel Tanner, Christian Lengeler

Correspondence to: Joanna R M Armstrong Schellenberg, Orchard Ground Cottage, Cublington, Bedfordshire LU7 OLJ, UK (e-mail:[email protected])

Insecticide-treated nets have proven efficacy as a malaria-control tool in Africa. However, the transition from efficacy to effectiveness cannot be taken for granted. We assessed coverage and the effect on child survival of a large-scale social marketing programme for insecticide-treated nets in two rural districts of southern Tanzania with high perennial malaria transmission.

Socially marketed insecticide-treated nets were introduced step-wise over a 2-year period from May, 1997, in a population of 480 000 people. Cross-sectional coverage surveys were done at baseline and after 1, 2, and 3 years. A demographic surveillance system (DSS) was set up in an area of 60 000 people to record population, births, and deaths. Within the DSS area, the effect of insecticide-treated nets on child survival was assessed by a case-control approach. Cases were deaths in children aged between 1 month and 4 years. Four controls for each case were chosen from the DSS database. Use of insecticide-treated nets and potential confounding factors were assessed by questionnaire. Individual effectiveness estimates from the case-control study were combined with coverage to estimate community effectiveness.

Insecticide-treated net coverage of infants in the DSS area rose from less than 10% at baseline to more than 50% 3 years later. Insecticide-treated nets were associated with a 27% increase in survival in children aged 1 month to 4 years (95% CI 3-45). Coverage in such children was higher in areas with longer access to the programme. The modest average coverage achieved by 1999 in the two districts (18% in children younger than 5 years) suggests that insecticide-treated nets prevented 1 in 20 child deaths at that time.

Interpretation: Social Marketing of insecticide-treated nets has great potential for effective malaria control in rural African settings.

Acta Trop 2001 Mar 30;78(3):191-206

Critical issues in the economic evaluation of interventions against communicable diseases.

Hutubessy RC, Bendib LM, Evans DB.

The Global Programme on Evidence for Health Policy, World Health Organization, 20 Avenue Appia, CH-1211 27, Geneva, Switzerland

Economic appraisal seeks to provide policy-makers with guidance about how scarce resources can be used to derive the greatest possible social benefit. Its use in the health sector has increased dramatically over the last decade although much of it has been focused on the problems of the more developed countries. The relatively sparse literature on communicable diseases has been dominated by interventions related to HIV/AIDS, hepatitis, malaria and tropical diseases. Reviews of this literature from the perspective of specific conditions such as Hepatitis B are already available, and recently the entire literature has been evaluated against the technical criteria for economic evaluations published in standard textbooks. Accordingly, this paper focuses on issues which would make economic appraisal more useful to policy-makers than it currently is. Given that few countries have the resources to undertake all the necessary analysis in their own settings, it is important that studies in one setting are undertaken in a way that allow generalisability to similar settings. Some of the most important challenges this poses for cost-effectiveness analysis (CEA) are identified. Firstly, incremental analysis is appropriate to local decision making when policy-makers are constrained to keep the current interventions and can consider only marginal improvements. However, it does not allow re-evaluation of existing interventions and is not transferable across settings. A version of Generalised CEA is proposed as an alternative. Secondly, data on costs and effectiveness are often not presented appropriately. The challenge for effectiveness is to adjust the evidence from efficacy studies to allow for different patient or population groups, and local variations in adherence, coverage, and infrastructure. For costs, it is important for studies to report the physical resources used in an intervention as well as unit prices. Thirdly, some long-term effects are still not well incorporated into CEA, especially those affecting child development and drug resistance. These questions are technically challenging and require more concerted efforts over the next few years. Finally, it is important for analysts to provide decision-makers with estimates of the resources that would be required to implement interventions claimed to be cost-effective. These improvements would better enable the evidence from economic analyses to enter the policy debate and be weighed against the other goals and objectives of the health system when allocating scarce resources.

PMID: 11311183 [PubMed – in process]

PubMed

J Infect Dis 2001 May 15;183(10):1530-1534

Plasmodium falciparum Induces a Th1/Th2 Disequilibrium, Favoring the Th1-Type Pathway, in the Human Placenta.

Fievet N, Moussa M, Tami G, Maubert B, Cot M, Deloron P, Chaouat G.

Research Unit 10, Mother and Child Health in the Tropics, Institut de Recherche pour le Developpement, Paris, France and Organisation de Coodination pour la Lutte contre les Endemies en Afrique Centrale, Yaounde, Cameroon.

During pregnancy, a local and systemic Th2 bias of maternal immunity favors Th1-dependent infections such as malaria. This study measured cytokines secreted in cultures of chorionic villi, placental blood cells (PBC), and serum in term placentas from 88 malaria-infected and -noninfected Cameroon women. Interleukin (IL)-2 and -4 were consistently low; IL-1beta, IL-6, granulocyte-macrophage colony-stimulating factor, and transforming growth factor (TGF)-beta2 were highest in villi cultures. Tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and IL-10 were highest in PBC cultures. Malaria placental infection increased Th1-type cytokines, whereas Th2-type cytokines and TGF-beta2 were unchanged. Addition of lipopolysaccharide or infected erythrocytes to cultures increased TNF-alpha, IL-1beta, IL-6, and IL-10 secretions but not those of IFN-gamma and IL-4. Overall, Plasmodium falciparum induced a placental immune response involving both Th1- and Th2-type cell activation. Although the Th1 pathway was favored, IL-10 secretion was also increased, and this increase should be effective in protecting the placenta by controlling the negative effects of Th1 cytokines on pregnancy.

Biometrics 1999 Jun;55(2):565-73

Stochastic algorithms for Markov models estimation with intermittent missing data.

Deltour I, Richardson S, Le Hesran JY.

INSERM U.170, Villejuif, France.

Multistate Markov models are frequently used to characterize disease processes, but their estimation from longitudinal data is often hampered by complex patterns of incompleteness. Two algorithms for estimating Markov chain models in the case of intermittent missing data in longitudinal studies, a stochastic EM algorithm and the Gibbs sampler, are described. The first can be viewed as a random perturbation of the EM algorithm and is appropriate when the M step is straightforward but the E step is computationally burdensome. It leads to a good approximation of the maximum likelihood estimates. The Gibbs sampler is used for a full Bayesian inference. The performances of the two algorithms are illustrated on two simulated data sets. A motivating example concerned with the modelling of the evolution of parasitemia by Plasmodium falciparum (malaria) in a cohort of 105 young children in Cameroon is described and briefly analyzed.

PMID: 11318215 [PubMed – in process]

Cent Afr J Med 2000 Jul;46(7):190-4

The efficacy and residual life span of two alphacypermethrin insecticide formulations (Fendona 6% suspension concentrate and Fendona Dry 15%) treated on mosquito bed nets.

Chirebvu E, Nzira L.

De Beers Research Laboratory, P O Box 197, Chiredzi, Zimbabwe. [email protected]

OBJECTIVE: To compare the effects of mosquito nets treated with two formulations of alpha-cypermethrin insecticide with a view to recommending the most appropriate formulation for use to treat mosquito nets. DESIGN: Assessment of insecticide potency under conditions of ordinary use. SETTING: Chilonga rural irrigation community in south east Lowveld Zimbabwe, a holoendemic area of year round malaria transmission. SUBJECTS: Convenience sample of 20 household heads (volunteers) was issued with treated mosquito nets. INTERVENTION: Following mosquito net treatment and distribution, bioassay tests were carried out monthly for a period of six months on insecticide and placebo treated nets. Questionnaires were administered once, one month post treatment of nets. MAIN OUTCOME MEASURES: Median mosquito knock down times of mosquitoes exposed to insecticide treated nets and community attitude towards the use of insecticide treated nets. RESULTS: Average time taken to knock down the median mosquito progressed from 2.3 minutes to 13.0 minutes for Fendona Dry 15% and from 4.1 minutes to 7.8 minutes for Fendona 6% SC over the six month period. The average time taken to knock down the median mosquito three months post-washing were 13.0 minutes and 7.4 minutes for Fendona Dry 15% and Fendona 6% SC respectively as against more than 30 minutes in controls. Both insecticides exhibited some wash resistance properties. The side effects reported were sneezing, itching, skin rash and smelling. Questionnaire data suggested that alphacypermethrin treated mosquito nets were welcomed. CONCLUSIONS: Both insecticide formulations proved to be suitable candidates. This was because of their insecticidal potency, wash resistance properties and acceptance by the community.

PMID: 11317588 [PubMed – in process]

Cent Afr J Med 2000 Jul;46(7):174-8

Urban malaria transmission in Mutare City; an unlikely phenomenon.

Masendu HT, McClean D, Mushavave ST, Chinyowa D, Simbanegavi P, Chawarika C, Ndlovu F.

Mutare City Health Department, Civic Centre, P O Box 910, Mutare.

OBJECTIVE: With an average altitude of 1,113 m above sea level and a mean maximum temperature of 28.6 degrees C, malaria transmission is possible in Mutare. Against transmission is the regular occurrence of ground frost. We reviewed epidemiological data and undertook a survey for the Anopheles vector. DESIGN: The Anopheles survey used standard techniques for sampling larvae and adult mosquitoes. Species identification was done by the polymerase chain reaction (PCR) technique. A random sample of blood slides was examined at the Blair Laboratory. Patient residence was determined from the outpatient register. Daily maximum and minimum temperatures monitored from the Mutare Fire Station, were obtained from the Meteorology Office in Harare. SETTING: Mutare city and suburbs. RESULTS: There was no evidence of rising temperatures in Mutare. Only non-vector Anopheles mosquitoes were identified (An. quadriannulatus and An. pretoriensis). One slide positive case had gametocytes present. Mapping generally showed no clustering, but there were two possible transmission foci. CONCLUSION: Temperatures are high enough, but winter lows (< 18 degrees C) do not support malaria transmission in Mutare. The Anopheles survey did not find the vector. Two suggestive clusters were mapped. While present data do not support ongoing malaria transmission within Mutare, in the past, An. gambiae, An. fenestus and An. pretoriensis were recorded. Careful monitoring will be needed.

PMID: 11317585 [PubMed – in process]

Parasitology 2001 Apr;122(Pt 4):379-91Plasmodium falciparum parasitaemia described by a new mathematical model.

Molineaux L, Diebner HH, Eichner M, Collins WE, Jeffery GM, Dietz K.

Department of Medical Biometry, University of Tubingen, Germany.

A new mathematical model of Plasmodium falciparum asexual parasitaemia is formulated and fitted to 35 malaria therapy cases making a spontaneous recovery after primary inoculation. Observed and simulated case-histories are compared with respect to 9 descriptive statistics. The simulated courses of parasitaemia are more realistic than any previously published. The model uses a discrete time-step of 2 days. Its realistic behaviour was achieved by the following combination of features (i) intra-clonal antigenic variation, (ii) large variations of the variants’ baseline growth rate, depending on both variant and case, (iii) innate autoregulation of the asexual parasite density, variable among cases, (iv) acquired variant-specific immunity and (v) acquired variant-transcending immunity, variable among cases. Aspects of the model’s internal behaviour, concerning variant dynamics, as well as the respective contributions of the three control mechanisms (iii) – (v), are displayed. Some implications for pathogenesis and control are discussed.

PMID: 11315171 [PubMed – in process]

Mem Inst Oswaldo Cruz 2001 Apr;96(3):427-33

Genome comparison of progressively drug resistant Plasmodium falciparum lines derived from drug sensitive clone.

Toteja R, Nair L, Bhasin V.

Department of Zoology, University of Delhi, Delhi, India.

Chloroquine has been the mainstay of malaria chemotherapy for the past five decades, but resistance is now widespread. Pyrimethamine or proguanil form an important component of some alternate drug combinations being used for treatment of uncomplicated Plasmodium falciparum infections in areas of chloroquine resistance. Both pyrimethamine and proguanil are dihydrofolate reductase (DHFR) inhibitors, the proguanil acting primarily through its major metabolite cycloguanil. Resistance to these drugs arises due to specific point mutations in the dhfr gene. Cross resistance between cycloguanil and pyrimethamine is not absolute. It is, therefore, important to investigate mutation rates in P. falciparum for pyrimethamine and proguanil so that DHFR inhibitor with less mutation rate is favored in drug combinations. Hence, we have compared mutation rates in P. falciparum genome for pyrimethamine and cycloguanil. Using erythrocytic stages of P. falciparum cultures, progressively drug resistant lines were selected in vitro and comparing their RFLP profile with a repeat sequence. Our finding suggests that pyrimethamine has higher mutation rate compared to cycloguanil. It enhances the degree of genomic polymorphism leading to diversity of natural parasite population which in turn is predisposes the parasites for faster selection of resistance to some other antimalarial drugs.

PMID: 11313656 [PubMed – in process]

Blood 2001 May 1;97(9):2879-2885

Molecular identification of Knops blood group polymorphisms found in long homologous region D of complement receptor 1.

Moulds JM, Zimmerman PA, Doumbo OK, Kassambara L, Sagara I, Diallo DA, Atkinson JP, Krych-Goldberg M, Hauhart RE, Hourcade DE, McNamara DT, Birmingham DJ, Rowe JA, Moulds JJ, Miller LH.

University of Texas-Houston Medical School, Houston; Case Western Reserve University, Cleveland, OH; University of Mali, Bamako, Mali; Washington University School of Medicine, St. Louis, MO; The Ohio State University, Columbus; University of Edinburgh, Scotland; Ortho Clinical Diagnostics, Raritan, NJ; and National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, MD.

Complement receptor 1 (CR1) has been implicated in rosetting of uninfected red blood cells to Plasmodium falciparum-infected cells, and rosette formation is associated with severe malaria. The Knops blood group (KN) is located on CR1 and some of these antigens, ie, McCoy (McC) and Swain-Langley (Sl(a)), show marked frequency differences between Caucasians and Africans. Thus, defining the molecular basis of these antigens may provide new insight into the mechanisms of P falciparum malaria. Monoclonal antibody epitope mapping and serologic inhibition studies using CR1 deletion constructs localized McC and Sl(a) to long homologous repeat D of CR1. Direct DNA sequencing of selected donors identified several single nucleotide polymorphisms in exon 29 coding for complement control protein modules 24 and 25. Two of these appeared to be blood group specific: McC associated with K1590E and Sl(a) with R1601G. These associations were confirmed by inhibition studies using allele-specific mutants. A sequence-specific oligonucleotide probe hybridization assay was developed to genotype several African populations and perform family inheritance studies. Concordance between the 1590 mutation and McC was 94%; that between Sl(a) and 1601 was 88%. All but 2 samples exhibiting discrepancies between the genotype and phenotype were found to be due to low red cell CR1 copy numbers, low or absent expression of some alleles, or heterozygosity combined with low normal levels of CR1. These data further explain the variability observed in previous serologic studies of CR1 and show that DNA and protein-based genetic studies will be needed to clarify the role of the KN antigens in malaria. (Blood. 2001;97:2879-2885)

PMID: 11313284 [PubMed – as supplied by publisher]

Sante 2001 Jan-Feb;11(1):25-33

The number of deaths attributable to malaria in the Niakhar area, Senegal, from 1984 to 1996

Ndiaye O, Hesran JY, Etard JF, Diallo A, Simondon F, Ward MN, Robert V.

Institut de recherche pour le developpement, BP 1386, Dakar, Senegal.

There are a number of reasons why climate, in certain physical and social environments, could have an impact on the epidemiology of malaria. Events, such as floods or drought, are related to the number of malaria cases and deaths, both seasonally and interannually. At a smaller scale, this study analyses the relation between climate variability and the variability in the number of deaths attributable to malaria in Niakhar, Senegal. The Niakhar area has a population of 30,000 and has been under demographic surveillance system since 1984. The rainfall in this region is highly seasonal, with a rainfall maximum in August and almost no rain between October/November and May/June. In addition to this seasonal cycle, rainfall also varies greatly from year to year (interannual variation). Over the 13 years, there were 661 deaths attributed to malaria with a marked interannual variability (range from 23 to 100, with a median of 43). There was also a strong seasonality in mortality, with nearly all deaths (89.1%) occurring between August and December. The number of deaths peaks in October, two months after the rainfall peak. Standardised monthly values were calculated for each climatic series (rainfall, relative humidity, temperature) as well as standardised five-month and monthly values of the number of deaths attributed to malaria between August and December. Correlation coefficients were calculated between these standardised values. The correlation between the variability in August rainfall and the variability in the number of deaths attributed to malaria between August and December was positive and statistically significant (r = +0.61, p = 0.02). In addition, highly significant cross-correlations were found between monthly rainfall series and monthly mortality series at one- and two-month lag (r = + 0.43, p = 0.0004 for one-month lag; r = + 0.26, p = 0.03 for two-month lag). This correlation is somewhat lower than the correlation of August rainfall alone with August to December mortality, but the result adds confidence to the signal given the increased degrees of freedom in the analysis. Similar, but slightly weaker, results were found when precipitation data were replaced with surface humidity data. Results with temperature were less clear; while temperature could in some circumstances have a direct impact on malaria, in this case here it is possible that the weak negative correlation between malaria deaths and temperature arises mainly because precipitation is physically connected to both the indices, correlating positively with malaria and negatively with temperature. The availability of a continuous demographic and medical survey since 1984 in a region of highly variable rainfall has created a rare opportunity to analyse with some confidence a climate versus malaria relationship. The findings are consistent with our understanding of the proposed link between rainfall and conditions for the reproduction of the malaria vector, leading to a lag time (here of one to two months) between anomalies of rainfall and deaths attributable to malaria. These results may have practical implications in Sub-Saharan regions marked by a great seasonal and interannual variability in rainfall by providing a simple tool to forecast the impact of climate variability on malaria mortality.

PMID: 11313229 [PubMed – in process]

Food Chem Toxicol 2001 May;39(5):407-22

Risk assessment of the use of deltamethrin on bednets for the prevention of malaria.

Barlow SM, Sullivan FM, Lines J.

Consultants in Toxicology, Harrington House, 8 Harrington Road, East Sussex BN1 6RE, Brighton, UK

Risk assessments covering the use of the pyrethroid, deltamethrin, on bednets for the prevention of malaria have been conducted The toxicity of deltamethrin in humans and animals is reviewed following both dermal and oral exposure. The no-adverse-effect level (NOEL) for exposure via the dermal route was 1000 mg/kg body weight/day. From this an acceptable exposure level (AEL) of 10 mg/kg body weight/day has been derived. The NOEL for exposure via the oral route was 1 mg/kg body weight/day, with exposures above this causing neurotoxic effects in animals. This NOEL has been used to derive margins of safety compared with predicted exposures. While direct skin contact does not seem to cause systemic toxicity in humans, it can cause burning, numbness and tingling of the skin, which is a local effect. This too is taken into account in the risk assessments. The risk assessments cover those treating bednets, on an intermittent or regular basis, the washing of treated nets, sleeping under treated nets (infants, children and adults). Worst case scenarios for each of these situations show that dermal exposures are low (one-tenth or less of the AEL) and the margins of safety for systemic exposure derived from oral data are acceptable, ranging from 10 to 3300. The benefits of the use of treated bednets in reducing morbidity and mortality from malaria are considerable and it can be concluded that the risk:benefit ratio is very favourable.

PMID: 11313107 [PubMed – in process]

Exp Parasitol 2001 Mar;97(3):119-28

Primary Structure of the Plasmodium vivax crk2 Gene and Interference of the Yeast Cell Cycle upon Its Conditional Expression.

Speranca MA, Vinkenoog R, Ocampos M, Fischer K, Janse CJ, Waters AP, del Portillo HA.

Departamento de Parasitologia, Instituto de Ciencias Biomedicas, Sao Paulo, SP, 05508-900, Brazil

Speranca, M. A., Vinkenoog, R., Ocampos, M., Fischer, K., Janse, C. J., Waters, A. P., and del Portillo, H. A. 2001. Primary structure of the Plasmodium vivax crk2 gene and interference of the yeast cell cycle upon its conditional expression. Experimental Parasitology 97, 119-128. The cdc2 gene product, a 34-kDa protein kinase, plays a universal role in the M phase of the eukaryotic cell cycle. To study the cell cycle regulation in malarial parasites, we have characterized a cdc2-related gene from the most widely distributed human malaria, Plasmodium vivax (Pvcrk2). The full-length Pvcrk2 revealed 90-99% homology with Crk2 proteins from other Plasmodium species and approximately 60% homology with p34(cdc2) proteins from higher eukaryotes. We used the temperature-sensitive Schizosaccharomyces pombe cdc2 mutant (cdc2-33(ts)) for gene complementation studies. Expression of the full-length 33-kDa PvCrk2 protein, a truncated 27-kDa version, and two chimeric proteins in which we exchanged the N- and C-terminal regions of PvCrk2 with their S. pombe counterparts at the restrictive temperature in the mutant cdc2-33(ts) did not complement the cell cycle defect. However, conditional expression of the Pvcrk2 genes or the chimera containing the C terminus from Spcdc2 in mutant cdc2-33(ts) cells produced cell-cycle-arrested phenotypes only in the induced state and at the permissive temperature. Our results thus provide the first compelling genetic evidence that the plasmodial Crk2 gene product(s) is capable of interfering with the well-conserved eukaryotic cell cycle machinery. Copyright 2001 Academic Press.

PMID: 11312574 [PubMed – in process]

 Biochem J 2001 May 1;355(Pt 3):733-9

Transport of lactate and pyruvate in the intraerythrocytic malaria parasite, Plasmodium falciparum.

Elliott JL, Saliba KJ, Kirk K.

School of Biochemistry and Molecular Biology, Faculty of Science, Australian National University, Canberra, A.C.T. 0200, Australia.

The mature, intraerythrocytic form of the human malaria parasite, Plasmodium falciparum, is reliant on glycolysis for its energetic requirements. It produces large quantities of lactic acid, which have to be removed from the parasite’s cytosol to maintain the cell’s integrity and metabolic viability. Here we show that the monocarboxylates lactate and pyruvate are both transported across the parasite’s plasma membrane via a H(+)/monocarboxylate symport process that is saturable and inhibited by the bioflavonoid phloretin. The results provide direct evidence for the presence at the parasite surface of a H(+)-coupled monocarboxylate transporter with features in common with members of the MCT (monocarboxylate transporter) family of higher eukaryotes.

PMID: 11311136 [PubMed – in process]

Bioorg Med Chem 2001 Mar;9(3):785-92

Discovery of a novel lead structure for anti-malarials.

Wiesner J, Wissner P, Dahse HM, Jomaa H, Schlitzer M.

Biochemisches Institut der Universitatsklinik Giessen, Germany.

From a library of 61 compounds available from former studies 2,5-bis-acylaminobenzophenone 7p was identified as a lead structure for a novel class of anti-malaria agents active against multi-resistant Plasmodium falciparum strain Dd2. Some structural modifications of this initial lead demonstrated the potential for further improvement of the anti-plasmodial activity of this novel class of anti-malarials.

PMID: 11310613 [PubMed – in process]

J Assoc Physicians India 2000 Nov;48(11):1085-6

Relapse pattern of Plasmodium vivax in Mumbai: a study of 283 cases of vivax malaria.

Gogtay NJ, Desai S, Kadam VS, Kamtekar KD, Dalvi SS, Kshirsagar NA.

Department of Clinical Pharmacology, BYL Nair Ch Hospital & TN Medical College, Mumbai 400 008.

OBJECTIVES: To analyze the relapse pattern of Plasmodium vivax in the city of Mumbai. METHODS: 283 cases of smear positive vivax malaria were treated with full dose (25 mg/kg) chloroquine and were asked to follow up for at least one year. None of the patients received primaquine. RESULTS: Of the 150 cases who followed up for at least one year, 19 relapsed, 17/19 relapsed within the first 6 months; indicating that the relapse pattern in the city is predominantly of the tropical or Chesson strain type. CONCLUSIONS: Vivax malaria patients should be monitored for at least six months. Those who do relapse should receive treatment with full dose chloroquine and 14 days of primaquine treatment.

PMID: 11310387 [PubMed – in process]

J Clin Apheresis 2001;16(1):15-8

Erythrocytapheresis for Plasmodium falciparum infection complicated by cerebral malaria and hyperparasitemia.

Zhang Y, Telleria L, Vinetz JM, Yawn D, Rossmann S, Indrikovs AJ.

Department of Pathology, Blood Bank Division, University of Texas Medical Branch, Galveston, Texas.

In malaria due to Plasmodium falciparum, life-threatening complications are in part related to the degree of parasitemia. Whole blood exchange and red blood cell exchange (RCE) have been used for the rapid removal of parasites from the circulation of patients with a high parasite load complicated by cerebral, pulmonary, and renal dysfunction. We have treated three 5-45-year-old patients with hyperparasitemia and end-organ dysfunction with red cell exchange by automated apheresis as an adjunct to specific anti-malarial chemotherapy. Parasitemia dropped more than 80% in all three patients immediately after the exchange, and all patients had an uneventful and full recovery. In combination with effective anti-malarial chemotherapy, apheresis RCE is a safe and rapid approach to treat complicated malaria due to P. falciparum. J. Clin. Apheresis. 16:15-18, 2001. Copyright 2001 Wiley-Liss, Inc.

PMID: 11309825 [PubMed – in process]

 Proc Natl Acad Sci U S A 2001 Apr 24;98(9):5228-5233

Anti-mosquito midgut antibodies block development of Plasmodium falciparum and Plasmodium vivax in multiple species of Anopheles mosquitoes and reduce vector fecundity and survivorship.

Lal AA, Patterson PS, Sacci JB, Vaughan JA, Paul C, Collins WE, Wirtz RA, Azad AF.

Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Chamblee, GA 30341; Department of Microbiology and Immunology, University of Maryland, 655 West Baltimore Street, Baltimore, MD 21201; and Malaria Program, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910.

The mosquito midgut plays a central role in the sporogonic development of malaria parasites. We have found that polyclonal sera, produced against mosquito midguts, blocked the passage of Plasmodium falciparum ookinetes across the midgut, leading to a significant reduction of infections in mosquitoes. Anti-midgut mAbs were produced that display broad-spectrum activity, blocking parasite development of both P. falciparum and Plasmodium vivax parasites in five different species of mosquitoes. In addition to their parasite transmission-blocking activity, these mAbs also reduced mosquito survivorship and fecundity. These results reveal that mosquito midgut-based antibodies have the potential to reduce malaria transmission in a synergistic manner by lowering both vector competence, through transmission-blocking effects on parasite development, and vector abundance, by decreasing mosquito survivorship and egg laying capacity. Because the intervention can block transmission of different malaria parasite species in various species of mosquitoes, vaccines against such midgut receptors may block malaria transmission worldwide.

PMID: 11309510 [PubMed – as supplied by publisher]

Parasite Immunol 2001 May;23(5):267-9

CD1d-restricted NK T cells are dispensable for specific antibody responses and protective immunity against liver stage malaria infection in mice.

Romero JF, Eberl G, MacDonald Hr, Corradin G.

Institute of Biochemistry and Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.

Immunization with a single dose of irradiated sporozoites is sufficient to induce protection against malaria in wild-type mice. Although this protection is classically attributed to conventional CD4+ and CD8+ T cells, several recent reports have suggested an important role for CD1-restricted NK T cells in immunity to malaria. In this study, we directly compared the ability of C57BL/6 wild-type and CD1-deficient mice to mount a protective immune response against Plasmodium berghei sporozoites. Our data indicate that CD1-restricted NK T cells are not required for protection in this model system. Moreover, specific IgG antibody responses to the P. berghei circumsporozoite repeat sequence were also unaffected by CD1 deficiency. Collectively, our data demonstrate that CD1-restricted NK T cells are dispensable for protective immunity to liver stage P. berghei infection.