28.01.2008
WE CAN’T AFFORD TO WAIT:
The Business Case for Rapid Scale-up of Malaria Control in Africa [January 2008] — (English)
Report prepared by Malaria No More and McKinsey & Company on behalf of the Roll
Back Malaria Partnership...
Tropenkrankheiten verbreiten sich durch Klimawandel
[e+dizin - Germany] — (Deutsch)
Eine der gefürchtetsten Tropenkrankheiten, die Malaria, wird durch den Stich von Anopheles-Mücken übertragen. Diese Tiere benötigen nicht nur warme Lufttemperaturen zum Überleben, sondern auch warme stehende Gewässer, um sich fortzupflanzen. Durch die Erderwärmung wird vermutlich nicht nur der Mittelmeerraum den Insekten in Zukunft zusätzliche ideale Lebens- und Brutbedingungen bieten. Der Gesundheitsexperte Professor Anthony McMichael von der Australian National University hat jetzt gegenüber dem "British Medical Journal" erklärt, dass seinen Schätzungen zufolge im Jahre 2080 weltweit zwischen 20 und 70 Millionen mehr Menschen in Malaria-Risikogebieten leben werden als heute...
26.01.2008
Baldness getting more attention than Malaria: Gates [Hindu - Chennai,India] — (English)
Lauding the efforts of corporate sector in improving lives of millions of people world-wide, Microsoft chairman William Gates said the "capitalism" needs to pay more attention to the neglected communities living in poverty. "Cures for malaria, which kills over a million a year, receive less attention than cures for baldness," Gates said, while addressing CEOs and political leaders at World Economic Forum meeting here...
Banning of DDT unleashed malaria [The Kingston Whig-Standard - Kingston, Ontario, Canada] — (English)
It's a wonderful campaign that nurse Debra Lefebvre is spearheading. I'm sure the mosquito nets her group sends will help save many lives in Africa and around the world. But I can't help but reflect on the root cause of these needless deaths...
25.01.2008
A tool box for operational mosquito larval control: preliminary results and early lessons from the Urban Malaria Control Programme in Dar es Salaam, Tanzania [Malaria Journal 2008, 7:20 (25 January 2008)] — (English)
A programme which delegates responsibility for routine mosquito control and surveillance to modestly-paid community members. This pilot study addresses some of the important issues of larviciding in an urban environment...
Gambia: New Malaria Drug Set for Use [The Daily Observer (Banjul) via allAfrica.com] — (English)
The Gambia, on Wednesday, ventured officially into using a new drug in malaria treatment called Coartem, following studies across the country showing resistance to chloroquine (CQ) exceeding levels recommended by the World Health Organisation globally...
Malaria spraying in full swing [Republic of Botswana - Gaberones,Botswana] — (English)
Following the recent heavy rains that have enveloped Botswana, Tutume Sub-district, as one of the five malaria-prone areas in the country, has already started spraying for the disease carrying mosquito...
24.01.2008
$11bn needed for malaria control [Financial Times - London,England,UK] — (English)
A group of government and business leaders will on Friday unveil a plan to sharply reduce the impact of malaria in the developing world. The Malaria Implementation Support Team plans to rapidly boost prevention and treatment measures in the 30 African countries most hard hit by malaria, which causes more than a million deaths and very large numbers of hospital admissions each year...
A new malaria vaccine looked strong in a small trial conducted in Mali by a team of international researchers [Science Daily - USA] — (English)
University of Navarra PhD in chemistry researcher, Esther Vicente, has discovered new compounds active for treating tuberculosis and malaria. Her thesis, defended at the Faculty of Sciences in her home city of Pamplona, the capital of Navarre, describes the synthesis and characterisation of 65 derivatives of quinoxaline, the structure of which is similar to a number of antimalalarial and antituberculosis pharmaceutical drugs currently on the market. Of the molecules prepared, four stand out for their antimalalarial activity and 15 for their antituberculosis activity...
Early Promising Results In Malaria Vaccine Trial [Science Daily - US] — (English)
A small clinical trial conducted by an international team of researchers in Mali has found that a candidate malaria vaccine was safe and elicited strong immune responses in the 40 Malian adults who received it...
GlaxoSmithKline and Medicines For Malaria Venture announce new collaboration to investigate novel antimalarial compounds [GSK Press Release] — (English)
GlaxoSmithKline (GSK) and the not-for-profit group, Medicines for Malaria Venture (MMV), today announced a new collaboration to identify novel drugs for the treatment of malaria. Research will focus on macrolide antibiotics, based on azithromycin, which may have promise as an antimalarial treatment. Under the new agreement, MMV will provide funding for research to be performed at GSK...
Characterization of two putative potassium channels in Plasmodium falciparum [Malaria Journal 2008, 7:19 (24 January 2008)] — (English)
Potassium channels identified by in silico sequence analyses and confirmed by immunocytochemical methods...
How colonialism & imperialism spread malaria [Workers World - USA] — (English)
A Review of “The Making of a Tropical Disease: A Short History of Malaria” by Randall M. Packard (Johns Hopkins Biographies of Disease)...
Africa: Malaria Kills 3000 Children Everyday [Ghanaian Chronicle (Accra)] — (English)
Available statistics has it that the most affected victims of malaria are women and children...
23.01.2008
Safety and Immunogenicity of an AMA-1 Malaria Vaccine in Malian Adults: Results of a Phase 1 Randomized Controlled Trial [PLoS ONE] — (English)
The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site...
A Trial of the Efficacy, Safety and Impact on Drug Resistance of Four Drug Regimens for Seasonal Intermittent Preventive Treatment for Malaria in Senegalese Children [PLoS ONE] — (English)
Monthly treatment with SP+3AQ is a highly effective regimen for seasonal IPT. Choice of this regimen would minimise the spread of drug resistance and allow artemisinins to be reserved for the treatment of acute clinical malaria...
Malaria Vaccine Shows Promise in Small Trial [Washington Post - USA] — (English)
A new malaria vaccine looked strong in a small trial conducted in Mali by a team of international researchers...
GSK gets charity money for R&D [Financial Times - UK] — (English)
Two charities have agreed to pay several million dollars to GlaxoSmithKline to help finance the development of new medicines for infectious diseases. The Medicines for Malaria Venture and the TB Alliance, two non-profit drug development partnerships substantially supported by the Bill & Melinda Gates Foundation, announced expanded funding to GSK on Thursday...
The effects of a partitioned var gene repertoire of Plasmodium falciparum on antigenic diversity and the acquisition of clinical immunity [Malaria Journal 2008, 7:18 (23 January 2008)] — (English)
Recombination hierarchies within the var gene repertoire of P.falciparum have a severe effect on strain diversity and the process of acquired immunity against malaria. Future studies will show how the existence of these recombining groups can offer an evolutionary advantage in spite of their restriction on diversity...
Multiplicity of Plasmodium falciparum infection in asymptomatic children in Senegal: relation to transmission, age and erythrocyte variants [Malaria Journal] — (English)
Based on data was gathered in a field survey in Senegal, the study describes the complexity of malaria infections in relation to genetic host factors, particularly thalassaemia...
Malaria Mortality "Sharply" Declines in Ethiopia [Africa Leader - USA] — (English)
Mortality from malaria has sharply declined following the concerted campaign conducted to prevent and control malaria during the millennium, the Ministry of Health said...
TGF to pump Rs 22m into malaria control programme [Daily Times - Lahore,Pakistan] — (English)
The Health Ministry Directorate of Malaria Control Programme (DMCP) will receive Rs 22 million from The Global Fund (TGF) that is funding the international fight against AIDS, tuberculosis and malaria...
Angola: Bié - l'OMS intensifie les mesures de lutte contre la malaria [Angola Press Agency (Luanda) via allAfrica.com] — (Français)
L'Organisation Mondiale de la Santé(OMS), en partenariat avec la direction de la santé de Bié, intensifie ces derniers temps, au niveau de la province, les mesures de lutte contre le paludisme, a informé mercredi, son représentant local, Lelo Zola...
22.01.2008
Fatal malaria strain 'mistaken for more benign form' [SciDev.Net - UK] — (English)
potentially fatal form of malaria is often mistaken for a less serious form of the disease, say researchers in Malaysia. They warn that doctors throughout South-East Asia must be more alert to the problem...
Erster Malaria-Impfstoff für Babys in Sicht [Ärzte Zeitung - Deutschland] — (English)
Auf dem Weg zu einem Malaria-Impfstoff für Entwicklungsländer sind Forscher einen großen Schritt weitergekommen. Ein Impfstoff mit Sporozoiten- Antigenen (RTS,S) hat sich in einer Studie mit Säuglingen als sicher und immunogen erwiesen...
Nigeria: NRCS, Esso Mobil, Others Walk Against Malaria [Vanguard (Lagos) via allAfrica.com] — (English)
A walk for life was the theme of a walk held last week in Lagos. The event was the 2nd phase of the 3rd Integrated Roll Back Malaria (RBM) awareness campaign which took place in some vulnerable communities in Lagos last week...
Articles requiring subscription
Using evolutionary costs to enhance the efficacy of malaria control via genetically manipulated mosquitoes [Parasitology. 2008 Jan 24] — (English)
An earlier mathematical model exploring the use of genetically manipulated mosquitoes for malaria control suggested that the prevalence of malaria is reduced significantly only if almost all mosquitoes become completely resistant to malaria. Central to the model was the 'cost of resistance': the reduction of a resistant mosquito's evolutionary fitness in comparison with a sensitive one's. Here, we consider the possibility of obtaining more optimistic outcomes by taking into account the epidemiological (in addition to the evolutionary) consequences of a cost of resistance that decreases the life-span of adult mosquitoes (the most relevant parameter for the parasite's epidemiology). There are two main results. First, if despite its cost, resistance is fixed in the population, increasing the cost of resistance decreases the intensity of transmission. However, this epidemiological effect is weak if resistance is effective enough to be considered relevant for control. Second, if the cost of resistance prevents its fixation, increasing it intensifies transmission. Thus, the epidemiological effect of the cost of resistance cannot compensate for the lower frequency of resistant mosquitoes in the population. Overall, our conclusion remains pessimistic: so that genetic manipulation can become a promising method of malaria control, we need techniques that enable almost all mosquitoes to be almost completely resistant to infection...
The molecular basis of chloroquine block of the inward rectifier Kir2.1 channel [Proc Natl Acad Sci U S A. 2008 Jan 23] — (English)
Although chloroquine remains an important therapeutic agent for treatment of malaria in many parts of the world, its safety margin is very narrow. Chloroquine inhibits the cardiac inward rectifier K(+) current I(K1) and can induce lethal ventricular arrhythmias. In this study, we characterized the biophysical and molecular basis of chloroquine block of Kir2.1 channels that underlie cardiac I(K1). The voltage- and K(+)-dependence of chloroquine block implied that the binding site was located within the ion-conduction pathway. Site-directed mutagenesis revealed the location of the chloroquine-binding site within the cytoplasmic pore domain rather than within the transmembrane pore. Molecular modeling suggested that chloroquine blocks Kir2.1 channels by plugging the cytoplasmic conduction pathway, stabilized by negatively charged and aromatic amino acids within a central pocket. Unlike most ion-channel blockers, chloroquine does not bind within the transmembrane pore and thus can reach its binding site, even while polyamines remain deeper within the channel vestibule. These findings explain how a relatively low-affinity blocker like chloroquine can effectively block I(K1) even in the presence of high-affinity endogenous blockers. Moreover, our findings provide the structural framework for the design of safer, alternative compounds that are devoid of Kir2.1-blocking properties...
Drug-resistant malaria parasites introduced into Madagascar from Comoros Islands [Emerg Infect Dis. 2007 Nov;13(11):1759-62] — (English)
To determine risk for drug-resistant malaria parasites entering Madagascar from Comoros Islands, we screened travelers. For the 141 Plasmodium falciparum isolates detected by real-time PCR, frequency of mutant alleles of genes associated with resistance to chloroquine and pyrimethamine was high. International-level antimalarial policy and a regional antimalarial forum are needed...
A comprehensive model of purine uptake by the malaria parasite Plasmodium falciparum: identification of four purine transport activities in intraerythrocytic parasites [Biochem J. 2008 Jan 11] — (English)
Plasmodium falciparum is incapable of de novo purine biosynthesis, and is absolutely dependent on transporters to salvage purines from the environment. Only one low-affinity adenosine transporter has been characterised to date. Here we report a comprehensive study of purine nucleobase and nucleoside transport by intraerythrocytic P. falciparum parasites. Isolated trophozoites expressed (a) a high affinity hypoxanthine transporter with a secondary capacity for purine nucleosides, (b) a separate high affinity transporter for adenine (c) a low affinity adenosine transporter and (d) a low affinity/high capacity adenine carrier. Hypoxanthine was taken up with 12-fold higher efficiency than adenosine. Using a parasite clone with a disrupted PfNT1 gene we found that the high affinity hypoxanthine/nucleoside transport activity was completely abolished whereas the low affinity adenosine transport activity was unchanged. Adenine transport was increased, presumably to partly compensate for the loss of the high affinity hypoxanthine transporter. We thus propose a model for purine salvage in P. falciparum, based on the highly efficient uptake of hypoxanthine by PfNT1 and a high capacity for purine nucleoside uptake by a lower affinity carrier...
New active drugs against liver stages of Plasmodium predicted by Molecular Topology [Antimicrob Agents Chemother. 2008 Jan 22] — (English)
We conducted a quantitative structure-activity relationship (QSAR) study based on a database of 127 compounds previously tested against the liver stage of Plasmodium yoelii, in order to develop a model capable of predicting the in vitro antimalarial activity of new compounds. Topological indices were used as structural descriptors, and their relation to antimalarial activity was determined by using linear discriminant analysis (LDA). A topological model consisting of two discriminant functions was created. The first function discriminated between active and inactive compounds, and the second identified the most active amongst the active compounds. The model was then applied sequentially to a large database of compounds with unknown activity against liver stages of Plasmodium. Seventeen drugs that were predicted to be active or inactive were selected for testing against the hepatic stage of P. yoelii in vitro. Antiretroviral, antifungal and cardiotonic drugs were found to be highly active (nanomolar IC50 values), and two ionophores completely inhibited parasite development. The MTT assay was performed for all compounds on hepatocyte cultures and none of these compounds were toxic in vitro. For both ionophores, the same in vitro assay as for P. yoelii has confirmed their in vitro activity on P. falciparum. A similar topological model was used to estimate the octanol/water partition of each compound. These results demonstrate the utility of the QSAR and molecular topology approaches for identifying new drugs active against the hepatic stage of malaria parasites. We also show the remarkable efficacy of some drugs that were not previously reported to have antiparasitic activity...
Potent antimalarial activity of histone deacetylase inhibitor analogues [Antimicrob Agents Chemother. 2008 Jan 22] — (English)
The malaria parasite Plasmodium falciparum has at least five putative histone deacetylase enzymes (PfHDACs) which have been proposed as new antimalarial drug targets and may play roles in regulating gene transcription like the better known and more intensively studied human histone deacetylases (hHDACs). Fourteen new compounds derived from L-cysteine, or 2-aminosuberic acid, were designed to inhibit PfHDAC-1 based on homology modeling with human class I and II HDAC enzymes. The compounds displayed highly potent anti-proliferative activity against drug resistant (Dd2) or drug sensitive (3D7) strains of P. falciparum in vitro (IC50 3-334 nM). Unlike known hHDAC inhibitors, some of these new compounds were significantly more toxic to P. falciparum parasites than to mammalian cells. The compounds inhibited P. falciparum growth in erythrocytes at both the early and late stages of the parasite's life cycle and caused altered histone acetylation patterns (hyperacetylation) which is a marker of HDAC inhibition in mammalian cells. These results support PfHDAC enzymes as promising targets for new antimalarial drugs...
Duration of naturally acquired antibody responses to blood stage Plasmodium falciparum is age dependent and antigen specific [Infect Immun. 2008 Jan 22] — (English)
Naturally acquired antibody responses provide partial protection from clinical malaria, and blood stage vaccines under development aim to prime such responses. To investigate the determinants of antibody response longevity, serum IgG to several blood stage vaccine candidate antigens was examined in two cohorts of children aged up to 6 years during the dry seasons of 2003 and 2004 in The Gambia. The first cohort showed that most antibodies were lost within less than four months of the first sampling, if a persistent infection was not present, so the second year cohort involved sampling of individuals every 2 weeks over a three month period. Antibody responses in this second cohort were also influenced by persistent malaria infection, so analysis focused particularly on children who did not have parasites detected after the first time point. Antibodies to most antigens declined more slowly in the oldest age group of children (> 5 years old), and more rapidly in the youngest (< 3 years old). However, antibodies to merozoite surface protein 2 (MSP2) were shorter-lived and were not more persistent in older children. The age-specific and antigen-specific differences were not explained by different IgG subclass response profiles, indicating the probable importance of differential longevity of plasma cell populations rather than antibody molecules. It is likely that young children mostly have short-lived plasma cells and thus experience rapid decline in antibody levels, while older children have longer lasting antibody responses that depend on long-lived plasma cells...
Fetal responses during placental malaria modify the risk of low birth weight [Infect Immun. 2008 Jan 22] — (English)
Inflammation during placental malaria (PM) is associated with low birth weight (LBW), especially during first pregnancy, but the relative contribution of maternal or fetal factors that mediate this effect remains unclear, and the role of IFN-gamma has been controversial. We examined the relationship of maternal and cord plasma levels of IFN-gamma, TNF-alpha, IL-10, ferritin and leptin to birth weight among Tanzanian women delivering in an area of high malaria transmission. Placental levels of inflammatory cytokines including IFN-gamma increased significantly during PM of primigravid and multigravid women but not secundigravid women. PM also increased maternal peripheral levels of all inflammatory markers except IFN-gamma, but had strikingly little effect on cord levels of these proteins. In multivariate analysis, placental IFN-gamma was negatively associated (P = 0.01) and cord ferritin was positively associated (P < 0.0001) with birth weight in infected (PM+) first-time mothers. This relationship was absent in other mothers, consistent with the epidemiology of PM and disease. Cord leptin had a strong positive relationship with birth weight in offspring of PM- women (P = 0.02 to < 0.0001) but not PM+ women (all P = NS) from the three gravidity groups. The results confirm that placental IFN-gamma is related to LBW due to PM during first pregnancies, and suggest that fetal ferritin plays a protective role. Because fetal cells are a source of placental IFN-gamma and cord ferritin, the fetal response to PM may modify the risk of LBW...
In-Hospital Risk Estimation in Children with Malaria--Early Predictors of Morbidity and Mortality [Journal of Tropical Pediatrics Advance Access published online on January 22, 2008 ] — (English)
In our study, sMODS has been shown to represent a useful quantitative approach towards disease severity classification in resource poor settings and can be used for risk estimation in children suffering from malaria in terms of both morbidity and mortality...
Population structure of the malaria vector Anopheles darlingi in Rondônia, Brazilian Amazon, based on mitochondrial DNA [Mem Inst Oswaldo Cruz. 2007 Dec] — (English)
Anopheles darlingi is the most important Brazilian malaria vector, with a widespread distribution in the Amazon forest. Effective strategies for vector control could be better developed through knowledge of its genetic structure and gene flow among populations, to assess the vector diversity and competence in transmitting Plasmodium. The aim of this study was to assess the genetic diversity of An. darlingi collected at four locations in Porto Velho, by sequencing a fragment of the ND4 mitochondrial gene. From 218 individual mosquitoes, we obtained 20 different haplotypes with a diversity index of 0.756, equivalent to that found in other neotropical anophelines. The analysis did not demonstrate significant population structure. However, haplotype diversity within some populations seems to be over-represented, suggesting the presence of sub-populations, but the presence of highly represented haplotypes complicates this analysis. There was no clear correlation among genetic and geographical distance and there were differences in relation to seasonality, which is important for malarial epidemiology...
Naturally acquired antibodies to merozoite surface protein (MSP)-1(19) and cumulative exposure to Plasmodium falciparum and Plasmodium vivax in remote populations of the Amazon Basin of Brazil [Mem Inst Oswaldo Cruz. 2007 Dec;102(8):943-51] — (English)
To infer recent patterns of malaria transmission, we measured naturally acquired IgG antibodies to the conserved 19-kDa C-terminal region of the merozoite surface protein (MSP)-1 of both Plasmodium vivax (PvMSP-1(19)) and Plasmodium falciparum (PfMSP-1(19)) in remote malaria-exposed populations of the Amazon Basin. Community-based cross-sectional surveys were carried out between 2002 and 2003 in subjects of all age groups living along the margins of the Unini and Jaú rivers, Northwestern Brazil. We found high prevalence rates of IgG antibodies to PvMSP-1(19) (64.0 - 69.6%) and PfMSP-1(19) (51.6 - 52.0%), with significant differences in the proportion of subjects with antibodies to PvMSP-1(19) according to age, place of residence and habitual involvement in high-risk activities, defining some groups of highly exposed people who might be preferential targets of malaria control measures. In contrast, no risk factor other than age was significantly associated with seropositivity to PfMSP-1(19). Only 14.1% and 19.3% of the subjects tested for antibodies to PvMSP-1(19) and PfMSP-1(19) in consecutive surveys (142 - 203 days apart) seroconverted or had a three fold or higher increase in the levels of antibodies to these antigens. We discuss the extent to which serological data correlated with the classical malariometric indices and morbidity indicators measured in the studied population at the time of the seroprevalence surveys and highlight some limitations of serological data for epidemiological inference...
Retinoic Acid induced suicidal erythrocyte death [Cell Physiol Biochem. 2008;21(1-3):193-202] — (English)
Vitamin A and retinoic acid have previously been shown to confer some protection against a severe course of malaria by fostering the phagocytosis of parasitized erythrocytes. Phagocytosis of erythrocytes is stimulated by phosphatidylserine exposure at the cell surface. The present study has thus been performed to explore the effect of retinoic acid and the specific retinoic acid receptor (RAR) agonist 4-(E-2-[5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl]-1-propenyl) benzoic acid (TTNPB) on erythrocyte annexin V binding, which reflects phosphatidylserine exposure at the cell surface. A 24 hours exposure to either, retinoic acid (3 muM) or TTNPB (3 muM), indeed significantly increased annexin binding, an effect paralleled by decrease of forward scatter reflecting cell shrinkage. According to Fluo3 fluorescence, exposure to either, retinoic acid (10 muM, 24 hours) or TTNPB (10 muM, 6 hours), significantly increased cytosolic Ca(2+)-activity, a known trigger of phosphatidylserine exposure. Infection of erythrocytes with Plasmodium falciparum increased phosphatidylserine exposure, an effect increased in the presence of TTNPB. In conclusion, retinoid acid and TTNPB trigger phosphatididylserine exposure and cell shrinkage of erythrocytes, typical features of suicidal erythrocyte death or eryptosis. The eryptosis could participate in the accelerated clearance of parasitized erythrocytes from circulating blood following treatment with retinoids...
Ex Vivo Cytokine and Memory T Cell Responses to the 42-kDa Fragment of Plasmodium falciparum Merozoite Surface Protein-1 in Vaccinated Volunteers [The Journal of Immunology, 2008, 180: 1451-1461] — (English)
A number of blood-stage malaria Ags are under development as vaccine candidates, but knowledge of the cellular responses to these vaccines in humans is limited. We evaluated the nature and specificity of cellular responses in healthy American volunteers vaccinated with a portion of the major merozoite surface protein-1 (MSP1) of Plasmodium falciparum, MSP142, formulated on Alhydrogel. Volunteers were vaccinated three times with 80 µg of either MSP142-FVO/Alhydrogel or MSP142-3D7/Alhydrogel. Cells collected 2 wk after the third vaccination produced Th1 cytokines, including IFN- and IL-2 following Ag stimulation, and greater levels of the Th2 cytokines IL-5 and IL-13; the anti-inflammatory cytokine IL-10 and the molecule CD25 (IL-2R) were also detected. The volunteers were evaluated for the MSP142–FVO or MSP142-3D7 specificity of their T cell responses. Comparison of their responses to homologous and heterologous Ags showed ex vivo IFN- and IL-5 levels that were significantly higher to homologous rather than to heterologous Ags. The epitopes involved in this stimulation were shown to be present in the dimorphic MSP133 portion of the larger MSP142-3D7 polypeptide, and indirect experiment suggests the same for the MSP142–FVO polypeptide. This contrasts with B cell responses, which were primarily directed to the conserved MSP119 portion. Furthermore, we explored the maturation of memory T cells and found that 46% of vaccinees showed specific memory T cells defined as CD4+CD45RO+CD40L+ after long-term in vitro culture. The identification of human-specific CD4+ memory T cells provides the foundation for future studies of these cells both after vaccination and in field studies...
An alternative model for heme biosynthesis in the malarial parasite [Trends in Biochemical Sciences, Volume 32, Issue 10, October 2007, Pages 443-449] — (English)
The malarial parasite imports an infected host's red blood cell enzymes for heme biosynthesis during the intraerythrocytic stage. This is despite all the genes of the heme-biosynthetic pathway having been identified on the parasite genome. On the basis of predictions of parasite genome-coded enzyme localization, functionality of some of these enzymes and shuttling of intermediates between different parasite compartments, a hybrid model for parasite heme biosynthesis has been proposed. However, this model does not take into account the possible role of imported host enzymes in parasite heme biosynthesis. We propose an alternative model with an extrinsic heme-biosynthetic pathway in the parasite cytosol that uses imported host enzymes, and an intrinsic pathway confined to the organellar fractions that uses the parasite-genome-encoded enzymes...
Prepared in cooperation with WHO ANGOLA INFO.
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