Malaria: Where’s the problem?

4 Jan, 2012:  Wellcome Trust : Catherine Moyes






The spatial distribution of Plasmodium falciparum malaria endemicity in 2010.

Around 10,000 years ago, the population of Plasmodium falciparum (the parasite species responsible for most cases of malaria) rapidly expanded in Africa and spread worldwide, coincident with human population growth and subsequent diasporas facilitated by the dawn of agriculture. The disease reached out globally but since its height around the turn of the century in 1900, the borders have shrunk and malaria is now largely restricted to the tropics.
Today, malaria is a massive public health problem and occurs in more than 100 countries, inhabited by some 3.3 billion people – half of the world’s population. The logistics of tackling malaria are therefore extremely complicated. In 2005, a group of Wellcome Trust-funded researchers identified the need to know where malaria is in order to to effectively target malaria control measures. They also identified the need to quantify risk when mapping this disease. This is how the Malaria Atlas Project (MAP) was born.
The Malaria Atlas Project is based across four continents: Africa, Asia, Europe and the Americas. We have spent the last six years mapping the contemporary spatial limits and prevalence of the two most deadly strains of malaria – P. falciparum and Plasmodium vivax. Until this work started, malaria maps had either presented the results of parasite surveys or used environmental data to predict parasite prevalence. In the former instance, there are large areas that have never been surveyed, so no data is available. Using environmental data means that parasite prevalence can be predicted in all areas but this approach does not allow for the impact of malaria control measures.
We have developed models that are informed by both real parasite prevalence data and environmental data, and we have improved the models further by including factors such as urbanisation (mosquitoes generally prefer the countryside) and a sophisticated model of the effects of temperature. The outputs from our models predict malaria risk everywhere where the disease is common and can be used to create maps of risk. The most important use of our maps is to visualize the extent of the malaria problem today at global, regional or national scales.
But that is not the only use of our outputs. Further modeling work means that we can generate estimates of clinical burden and populations at risk, and provide national and province-level estimates. We used similar models to study the distribution of inherited blood disorders, whereas we found a very different modeling approach was required to map the mosquitoes that transmit malaria – information about mosquitoes typically comes in the form of occurrence data and it is usually presence rather than absence data that is available. Ecological niche modeling uses occurrence data, environmental variables and expert opinions to model the spatial distribution of a species and this is the approach we used to predict where the 41 dominant mosquito species that transmit malaria are found.
Ultimately our research has a strongly applied focus and aims to provide a sound evidence base for decision-making when planning which control measures to use and where to target scarce resources. With this in mind, we have placed all of our work on a new, freely accessible, web portal.
There you can find maps to download in high (.pdf) and low (.png) resolution formats, and if you are a GIS user you can download the surface data used to create these maps and make your own. Mathematical modellers can obtain our full model outputs to use in their own models and public health groups can obtain tables of estimates of burden and populations at risk.
At the moment the focus is on Plasmodium falciparum and the mosquitoes that transmit malaria but watch this space because there is much more to come over the next few months.

Catherine Moyes is Malaria Atlas Project Manager in the Spatial Ecology & Epidemiology Group at the University of Oxford.
Find out more about the Malaria Atlas Project and access its data and resources at http://www.map.ox.ac.uk

http://wellcometrust.wordpress.com/2012/01/04/malaria-wheres-the-problem/#more-8289

MALARIA: Plasmodium falciparum in the Peruvian Amazon

OraLee H. Branch*†,1, Patrick L. Sutton†,1, Carmen Barnes2, Juan Carlos Castro3,Julie Hussin4, Philip Awadalla4 and Gisely Hijar2
Abstract
Plasmodium falciparum entered into the Peruvian Amazon in 1994, sparking an epidemic between 1995 and 1998. Since 2000, there has been sustained low P. falciparum transmission. The Malaria Immunology and Genetics in the Amazon project has longitudinally followed members of the community of Zungarococha (N = 1,945, 4 villages) with active household and health center-based visits each year since 2003. We examined parasite population structure and traced the parasite genetic diversity temporally and spatially. We genotyped infections over 5 years (2003–2007) using 14 microsatellite (MS) markers scattered across ten different chromosomes. Despite low transmission, there was considerable genetic diversity, which we compared with other geographic regions. We detected 182 different haplotypes from 302 parasites in 217 infections. Structure v2.2 identified five clusters (subpopulations) of phylogenetically related clones. To consider genetic diversity on a more detailed level, we defined haplotype families (hapfams) by grouping haplotypes with three or less loci differences. We identified 34 different hapfams identified. The Fst statistic and heterozygosity analysis showed the five clusters were maintained in each village throughout this time. A minimum spanning network (MSN), stratified by the year of detection, showed that haplotypes within hapfams had allele differences and haplotypes within a cluster definition were more separated in the later years (2006–2007). We modeled hapfam detection and loss, accounting for sample size and stochastic fluctuations in frequencies overtime. Principle component analysis of genetic variation revealed patterns of genetic structure with time rather than village. The population structure, genetic diversity, appearance/disappearance of the different haplotypes from 2003 to 2007 provides a genome-wide “real-time” perspective of P. falciparum parasites in a low transmission region.

http://www.blogger.com/goog_1705683754

MALARIA: Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine against Malaria and Anemia in Pregnant Women

Nana O. Wilson*, Fatou K. Ceesay, Samuel A. Obed, Andrew A. Adjei, Richard K. Gyasi, Patricia Rodney, Yassa Ndjakani, Winston A. Anderson, Naomi W. Lucchi and Jonathan K. Stiles
Abstract.
The effectiveness of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) against malaria and anemia is unclear because of the spread of SP-resistant Plasmodium falciparum. This study evaluates the effectiveness of IPTp-SP among pregnant women attending the antenatal clinic at Korle-Bu Teaching Hospital in Accra, Ghana. A cross-sectional study comparing malaria and anemia prevalence among pregnant women using IPTp-SP with non-IPTp-SP users was conducted during June–August 2009. A total of 363 pregnant women (202 of IPTp users and 161 non-IPTp users) were recruited. A total of 15.3% of IPTp users had malaria compared with 44.7% of non-IPTp users (P < 0.001). A total of 58.4% of non-IPTp users were anemic compared with 22.8% of IPTp users (P < 0.001). When we controlled for other variables, the difference in the prevalence of malaria (odds ratio = 0.18, 95% confidence interval = 0.08–0.37) and anemia (odds ratio = 0.20, 95% confidence interval = 0.12–0.34) remained significant. The recommended IPTp-SP regimen is useful in preventing malaria and anemia among pregnant women in Ghana.

http://www.ajtmh.org/content/85/1/12.abstract

MALARIA: Why Is Plasmodium vivax a Neglected Tropical Disease?

Plasmodium vivax malaria is a debilitating, sometimes life-threatening, and economically repressive disease of many tropical and temperate countries outside Africa, and yet it is perceived as relatively benign. The estimated cost of the global burden of vivax malaria is US$1,400,000,000–$4,000,000,000 per year [1], and more people worldwide live at risk from P. vivax than P. falciparum [2]. All age groups suffer P. vivax infections and endure repeated, incapacitating febrile attacks, severe anemia, and respiratory distress, with poor outcomes in pregnancy and learning impairment in children also apparent. Similar to other neglected diseases, P. vivax affects primarily poor people lacking access to affordable health care, trapping many in a relentless cycle of poverty because of loss of adult productivity and depletion of meager financial reserves [3]–[5]. Global malaria elimination programs are mobilized against P. falciparum, most likely because of the greater mortality rates associated with it, and draw resources away from P. vivax even though vivax malaria is harder to prevent, diagnose, and treat, and both species are co-endemic. There is a consensus among malaria experts that eliminating P. vivax will prove more technically challenging than eliminating P. falciparum [6], and that there exist fewer tools and a weaker knowledge base from which to start an effective global elimination program [7].
http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0001160

MALARIA: History: Malaria, Protestants, and Google

Benjamin James Reilly
Did the Protestant Reformation inadvertently liberate Northern Europe from a long-standing demographic drain exerted by Rome's indigenous P. falciparum malaria? Perhaps, but the existing scholarship on Northern European travel to Rome is only suggestive, not conclusive. Although the presence of P. falciparum in Rome in historical times is well established, literature on Northern European travel to Rome draws from scattered and anecdotal evidence, thus rendering inconclusive their finding that Northern European travel to Rome declined after the Reformation. Seeking corroboration, I performed a statistical analysis of travel to Rome using a novel source: names taken from an archive of nearly 3,000 web pages generated by targeted search engine queries in three languages. The highly suggestive results obtained by this method not only support the original thesis, but also might serve as a guide for other scholars seeking data samples for untraditional environmental history research.
http://envhis.oxfordjournals.org/content/16/2/312.abstract?maxtoshow=&hits=18&RESULTFORMAT=&andorexacttitle=and&andorexacttitleabs=and&fulltext=malaria&andorexactfulltext=and&searchid=1&usestrictdates=yes&resourcetype=HWCIT&ct

MALARIA: Benign tertian malaria – a misnomer?

Chanaveerappa Bammigatti MBBS MD * Sirish Shetty MBBS MD Seema Shetty MBBS MD Ashwini Kumar MBBS MD
Plasmodium vivax usually causes an acute self-limiting febrile illness with fever spikes on every third day and no complications or death. Therefore the illness caused by this parasite was termed benign tertian malaria. However, many complications associatedwith Plasmodium falciparum have been seen with increasing frequency with Plasmodium vivax in recent times. The present study highlights the various complications associated with Plasmodium vivax malaria.
http://td.rsmjournals.com/cgi/content/abstract/

MALARIA: Kenya: Acute seizures attributable to falciparum malaria in an endemic area on the coast

Symon M. Kariuki1, Michelle Ikumi1, John Ojal, Manish Sadarangani1, Richard Idro1, Ally Olotu1, Philip Bejon1,, James A. Berkley1,, Kevin Marsh1,and Charles R. J. C. Newton1, Correspondence to: Symon M. Kariuki, Centre for Geographic Medicine Research-Coast, Kenya Medical Research Institute, Kilifi, Kenya, PO Box 230 Kilifi (80108), Kenya E-mail:skariuki@kilifi.kemri-wellcome.org
 January 28, 2011.

Summary
Falciparum malaria is an important cause of acute symptomatic seizures in children admitted to hospitals in sub-Saharan Africa, and these seizures are associated with neurological disabilities and epilepsy. However, it is difficult to determine the proportion of seizures attributable to malaria in endemic areas since a significant proportion of asymptomatic children have malaria parasitaemia. We studied children aged 0–13 years who had been admitted with a history of seizures to a rural Kenyan hospital between 2002 and 2008. We examined the changes in the incidence of seizures with the reduction of malaria. Logistic regression was used to model malaria-attributable fractions for seizures (the proportion of seizures caused by malaria) to determine if the observed decrease in acute symptomatic seizures was a measure of seizures that are attributable to malaria. The overall incidence of acute symptomatic seizures over the period was 651/100 000/year (95% confidence interval 632–670) and it was 400/100 000/year (95% confidence interval 385–415) for acute complex symptomatic seizures (convulsive status epilepticus, repetitive or focal) and 163/100 000/year (95% confidence interval 154–173) for febrile seizures. From 2002 to 2008, the incidence of all acute symptomatic seizures decreased by 809/100 000/year (69.2%) with 93.1% of this decrease in malaria-associated seizures. The decrease in the incidence of acute complex symptomatic seizures during the period was 111/100 000/year (57.2%) for convulsive status epilepticus, 440/100 000/year (73.7%) for repetitive seizures and 153/100 000/year (80.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures with parasitaemia were 92.9% (95% confidence interval 90.4–95.1%) for all acute symptomatic seizures, 92.9% (95% confidence interval 89.4–95.5%) for convulsive status epilepticus, 93.6% (95% confidence interval 90.9–95.9%) for repetitive seizures and 91.8% (95% confidence interval 85.6–95.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures in children above 6 months of age decreased with age. The observed decrease in all acute symptomatic seizures (809/100 000/year) was similar to the predicted decline (794/100 000/year) estimated by malaria-attributable fractions at the beginning of the study. In endemic areas, falciparum malaria is the most common cause of seizures and the risk for seizures in malaria decreases with age. The reduction in malaria has decreased the burden of seizures that are attributable to malaria and this could lead to reduced neurological disabilities and epilepsy in the area.

http://brain.oxfordjournals.org/content/134/5/1519.abstract

MALARIA: Africa: Cheap Malaria Drugs to Flood Africa Soon

Yinka Shokunbi : 30 April 2011
With the renewed determination of the international community to sweep out malaria out of Africa, a new initiative to put affordable and effective anti-malaria drugs within the reach of people in often remote communities in Africa is making rapid progress.
In four implementing countries - Ghana, Kenya, Madagascar and Nigeria - life-saving malaria treatment can now be bought in private stores and pharmacies for as little as 50 U.S. cents as against previous cost which was up to 20 times as much.
The Affordable Medicines Facility - malaria (AMFm) gets key financial support from UNITAD, the United Kingdom and the Bill & Melinda Gates Foundation, technical support from members of the Roll Back Malaria (RBM) Partnership and it is hosted by the Global Fund.
The initiative, which began last year, is being piloted in eight countries - Ghana, Kenya, Madagascar, Niger, Nigeria, Tanzania (including Zanzibar), Uganda and Cambodia - to enable lessons to be learnt before a potential global rollout.
AMFm aims to make anti-malarial drugs, known as artemisinin-based combination therapies (ACTs), available as widely and cheaply as possible. About 225 million people fall ill with malaria every year and 780,000 die from the disease.
Although the World Health Organisation (WHO) specifically recommends ACTs as first-line treatment for Plasmodium falciparum malaria, the most deadly form of the disease, the drug accounts for only about one in five of all treatments taken for malaria and until recently, it has only been available for free or at low cost in public health facilities.
Most people buy anti-malaria treatments in private shops and pharmacies where ACTs were not available at an affordable price before the launch of AMFm. These shops sell older, cheap medicines such as chloroquine and sulfadoxine-pyrimethamine, which are no longer effective because the Plasmodium falciparum is increasingly resistant to them.
The objective of the AMFm programme is to drive out these ineffective therapies by bringing down ACT treatment costs drastically and making the drugs more accessible to millions of people.
According to the executive director of the Global Fund, Prof. Michel Kazatchkine, "We are making further progress in fighting malaria in Africa by providing affordable treatment to millions of people through the Affordable Medicines Facility for malaria," said executive director of the Global Fund.
"The Affordable Medicines Facility - malaria is a major step forward. It uses innovative financing methods to save lives by providing affordable and effective medicines to more people in need through the public, NGO and private sectors."
For the innovation to work, the Global Fund first negotiates a discounted price for ACTs with drug manufacturers and then pays most of the reduced price on behalf of importers from the private, NGO and public sectors, leading to an average sales price of less than 10 cents.
The reduced prices allow private wholesalers to sell the ACTs to retailers at a profit. Pharmacies and stores in turn sell the drugs to patients and caregivers with an additional mark-up, while keeping the retail price affordable.
The AMFm was introduced in the country in March 2011, ACTs that are not co-paid by the AMFm cost about 1,000 - 1,500 Naira (US$ 6.70 - 9.50) per adult treatment.
The Society for Family Health (SFH), a not-for-profit NGO started distribution of AMFm co-paid ACTs in Nigeria in March 2011.
Under AMFm, SFH will sell a full course of treatment for children aged under-five years in private health facilities and outlets at US$ 0.20. The adult course of treatment is expected to sell for US$ 0.80.
In the eight countries where the AMFm is being implemented, governments are supporting the initiative with public awareness campaigns and training for ACT providers.
http://allafrica.com/stories/201105021732.html

MALARIA: WHO launches plan to contain resistance to artemisinin-based combination therapies

A WHO action plan outlines critical steps to ensure the effectiveness of the world’s most powerful treatment for malaria. The World Health Organization (WHO) has released its Global Plan for Artemisinin Resistance Containment (GPARC), which outlines the steps necessary to prevent the spread of artemisinin-resistant parasites and ensure the effectiveness of artemisinin-based combination therapies (ACTs) as the top-line medicine for treating malaria. Artemisinin-resistant parasites were first detected along the Thailand-Cambodia border several years ago; the WHO stresses that the world must now act quickly so that it does not lose the most effective existing treatment for Plasmodium falciparum malaria.
GPARC outlines five steps for preventing and containing artemisinin resistance:
    Stop the spread of resistant parasites.
    Increase monitoring and surveillance for artemisinin resistance.
    Improve access to malaria diagnostic testing and rational treatment with ACTs.
    Invest in artemisinin resistance-related research.
    Motivate action and mobilize resources.

The document is a companion to the Global Report on Antimalarial Drug Efficacy and Drug Resistance: 2000–2010, which provides the extensive evidence on which the GPARC was based.
http://www.macepalearningcommunity.org/newsletter_whoact.htm

MALARIA: New Mosquito Subgroup is Highly Susceptible to Malaria-Causing Parasites

Most studies of malaria vectors, such as Anopheles gambiae, have focused on mosquitoes that rest indoors, since they are more likely to have contact with humans and transmit the malaria parasite. Larval stage and outdoor-resting mosquitoes are not as well-studied because they are more difficult to find and collect.
Differences Between Outdoor- and Indoor-Resting Mosquitoes
Because outdoor- and indoor-resting mosquito subgroups live in such separate environments, they do not interbreed and have grown to differ genetically. For example, multiple recent studies have documented the beginnings of speciation between A. gambiae subgroups M and S, but this emerging speciation is taking place only among indoor-resting mosquitoes. In an NIAID-funded study published in February 2010 in the journal Science, researchers collected and genetically analyzed A. gambiae larvae from three village sites in Burkina Faso. The investigators were led by Kenneth Vernick, Ph.D., of the Institut Pasteur in Paris.

What These Differences Could Mean for Malaria Control
Analyzing the genomes of the larvae, they found two A. gambiae subgroups. One was genetically indistinguishable from indoor-resting adult mosquitoes in the Burkina Faso area, but the other did not match any subgroup of adult mosquitoes that had been described so far. The researchers found that mosquitoes belonging to this second group, named GOUNDRY after the area in which they were found, were much more susceptible to the parasite that causes malaria; the prevalence of Plasmodium falciparum infection among GOUNDRY mosquitoes was 58 percent, compared to 35 percent among the indoor-resting mosquitoes.
Although there is no evidence of GOUNDRY mosquitoes biting humans, any human feeding by these mosquitoes is of concern. Also, it should be noted that current malaria control measures such as bed nets and insecticide spraying focus on indoor-resting mosquitoes and are less effective against outdoor-resting subgroups.
http://www.niaid.nih.gov/topics/Malaria/research/Pages/newMosquitoSubgroup.aspx

MALARIA: Ghana: Malaria Day in Ghana, a reflection of the odds

25 April 2011
Hayford Siaw, Executive Director : Volunteer Partnerships for West Africa


According to the World Health Organization report on malaria in Ghana, US$27million and US$38million was spent on Malaria in 2008 and 2009 respectively. In spite of the huge amount of money invested, Ghana still recorded very worrying figures with 3,694,671 cases in 2009 compared to 3,200,147 in 2008. Admission to hospitals due to malaria also went up from 272,802 in 2008 to 277,047 in 2009. Death due to Malaria from the records of clinics and hospitals stood at 3,378 in 2009.
It must be noted that, the National Malaria Control Program (NMCP) is on record in it strategic plan that 70% of the Ghanaian population rely on traditional medicines. The absence of data from traditional medicine providers therefore should raise concern on the number of malaria deaths and sickness that goes unreported.
The increase in the scourge of malaria should be accepted as a failure on leadership responsible for controlling and or eliminating Malaria in Ghana. Indeed, the National Malaria Control strategic plan is a failed policy program and should therefore be re-examined. There is too much wastage on personnel instead of actual resources going into interventions that will help reduce both cases of admission and deaths. Over 30% of money allocated for Malaria Control went into Human Resources alone.
Historically malaria has been the cause of deaths all over the world. Of course it is no longer a threat to the developed world and has been modified in the developing countries with the exception of Sub-Saharan Africa where it is endemic. The United States was one of the first Western Counties to eliminate malaria, due to an extended campaign using surplus military aircraft left over from World War 2 which was equipped with insecticide dispersal systems necessary to dispense DDT as a Dust or liquid. This operation was a success and by 1950 only 5 years after the end of the war the Center for Disease Control in Atlanta Georgia, declared the United States malaria free.
Mr. Robert Desowitz in his book THE MALARIA CAPERS writes; from colonial times until the 1940s, malaria was the American disease. One of the first military expenditures of the Continental Congress was for $300 dollars to buy quinine to protect General Washingtons troops. During the Civil War one half of the white troops and four fifths of the black soldiers of the Union Army were stricken with malaria annually.
The malaria mosquito has the reputation of being 9 feet tall in Sub-Saharan Africa, more feared than the mighty crocodile. The truth be told, it is just an insignificant noisy insect, a biological creature, just like us. If the humble mosquito has the ability to infect humans with a parasite, humans should reciprocate in kind and infect the mosquito with an organism, to give as well as we get from this bane of mankind.
To be more specific, I would like to propose at this time we use a biological agent known as a fungus spore. There is a product in commercial production in the United States, used on organic farms that also have applications for the control of adult mosquitoes. Research done on malaria mosquitoes has indicated only one spore has the ability to kill a mosquito. Although it may take up to 10 days to kill the mosquito, after 2 days the mosquito no longer feeds. This product is a soil fungus, most soil insects are immune to its effects. However an airborne insect like the mosquito has no natural immunity to this spore and according to research done at UC Davis in California, the mosquito will never develop immunity to this fungus. When exposed the mosquitoes were 80 times less likely to transmit malaria.
According to Dr. Kenneth D. Vernick, a microbiologist at the University of Minnesota stated a soil fungus that devoured insects, whose mosquito-killing powers were described by British scientists last year, could be used to hunt down the most malaria-susceptible bugs in any swarm and knock them out of the gene pool. He also said for unknown reasons, it weakens plasmodium-carrying mosquitoes more than it does others. Even after exposure to a 12 day old spray, 89% of the mosquitoes died.
This is good news as plasmodium falciparum is the most dangerous parasite of the four malaria parasites that infect man and the most prevalent by far in Ghana where it comprises up to 98% of infections.
This is all fine and dandy you might say, however, how is this fungus spore to be delivered to the recipient, the malaria mosquito? The same way the Americans did it 60 years ago, using aircraft equipped with insecticide, aerosol generators. This is the only effective method.
WHO writes in it 2010 report on Ghana, ‘’there is no evidence of a reduction in suspected malaria cases between 2000 and 2009, while inpatient cases in all ages increased’’.
http://www.ghanaweb.com/GhanaHomePage/NewsArchive/artikel.php?ID=207445

MALARIA: Doxycycline for Malaria Chemoprophylaxis and Treatment:

Doxycycline for Malaria Chemoprophylaxis and Treatment: Report from the CDC Expert Meeting on Malaria Chemoprophylaxis
Kathrine R. Tan*, Alan J. Magill, Monica E. Parise, AND Paul M. Arguin
Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia; Walter Reed Army Institute for Research, Silver Spring, Maryland

Abstract.:
Doxycycline, a synthetically derived tetracycline, is a partially efficacious causal prophylactic (liver stage of Plasmodium) drug and a slow acting blood schizontocidal agent highly effective for the prevention of malaria. When used in conjunction with a fast acting schizontocidal agent, it is also highly effective for malaria treatment. Doxycycline is especially useful as a prophylaxis in areas with chloroquine and multidrug-resistant Plasmodium falciparum malaria. Although not recommended for pregnant women and children < 8 years of age, severe adverse events are rarely reported for doxycycline. This report examines the evidence behind current recommendations for the use of doxycycline for malaria and summarizes the available literature on its safety and tolerability.
http://www.ajtmh.org/cgi/content/abstract/84/4/517?maxtoshow=&hits=23&RESULTFORMAT=&andorexacttitle=and&andorexacttitleabs=and&fulltext=malaria&andorexactfulltext=and&searchid=1&usestrictdates=yes&resourcetype=HWCIT&ct

Artemisinin combination therapy for vivax malaria

The Lancet Infectious Diseases : Volume 10, Issue 6, June 2010, Pages 405-416 PubMed ID: 20510281
Douglas, N.M.a b , Anstey, N.M.a b , Angus, B.J.b , Nosten, F.b d e , Price, R.N.a b c
Early parasitological diagnosis and treatment with artemisinin-based combination therapies (ACTs) are key components of worldwide malaria elimination programmes. In general, use of ACTs has been limited to patients with falciparum malaria whereas blood-stage infections with Plasmodium vivax are mostly still treated with chloroquine. We review the evidence for the relative benefits and disadvantages of the existing separate treatment approach versus a unified ACT-based strategy for treating Plasmodium falciparum and P vivax infections in regions where both species are endemic (co-endemic). The separate treatment scenario is justifiable if P vivax remains sensitive to chloroquine and diagnostic tests reliably distinguish P vivax from P falciparum. However, with the high number of misdiagnoses in routine practice and the rise and spread of chloroquine-resistant P vivax, there might be a compelling rationale for a unified ACT-based strategy for vivax and falciparum malaria in all co-endemic regions. Analyses of the cost-effectiveness of ACTs for both Plasmodium species are needed to assess the role of these drugs in the control and elimination of vivax malaria.
http://www.scopus.com/record/display.url?eid=2-s2.0-77952605533&origin=inward&txGid=xIxHwce1_VFPqFnB8SYQw0y%3a2

MALARIA: Prevalence of Plasmodium falciparum infection in asymptomatic rural Gabonese populations

Nkoghe D, Akue J, Gonzalez J, Leroy EM
Background
Malaria may be perennial or epidemic in sub-Saharan Africa, and its transmission may be stable or unstable, depending on the region. The prevalence of asymptomatic Plasmodium falciparum carriage is poorly documented in Gabon. A large survey of P. falciparum infection was conducted in asymptomatic individuals living in rural Gabon.

Methods
Two hundred and twenty-two villages were randomly selected in the nine administrative regions. With the participants' informed consent, blood samples were collected for thick and thin blood film examination after 20% Giemsa staining. Prevalence rates were calculated per village, per region and per ecosystem, and nationwide. Demographic risk factors were identified with STATA software version 9.0. Significance was assumed at p<0.05.

Results and discussion
The prevalence of P. falciparum in adults was 6.2% (269/4342) nationwide, with a maximum of 37.2% in one village; a linear decrease was observed with increasing age (p= 0.045). Only 5% of the 399 children from forest areas tested positive. The prevalence was significantly higher in forest areas (7%) than in savannah (4%) and lakeland (2.5%). Within the forest region, the prevalence was significantly higher in forest grassland (10.9%) than in the mountain forest (3.5%), interior forest (6.8%) and north-eastern forest (4.5%).

Conclusion
Plasmodium falciparum carriage remains high among adults in rural Gabon. Control measures must be adapted to the region and ecosystem. Routine treatment of asymptomatic individuals should be considered

Malaria Journal 2011, 10:33 (9 February 2011)

MALARIA: Central carbon metabolism of Plasmodium parasites

01 February 2011 : Molecular and Biochemical Parasitology : Kellen L. Olszewski, Manuel Llinás


The central role of metabolic perturbation to the pathology of malaria,the promise of antimetabolites as antimalarial drugs and a basic scientific interest in understanding this fascinating example of highly divergent microbial metabolism has spurred a major and concerted research effort towards elucidating the metabolic network of the Plasmodium parasites. Central carbon metabolism, broadly comprising the flow of carbon from nutrients into biomass, has been a particular focus due to clear and early indications that it plays an essential role in this network. Decades of painstaking efforts have significantly clarified our understanding of these pathways of carbon flux, and this foundational knowledge, coupled with the advent of advanced analytical technologies, have set the stage for the development of a holistic, network-level model of plasmodial carbon metabolism. In this review we summarize the current state of knowledge regarding central carbon metabolism and suggest future avenues of research. We focus primarily on the blood stages of Plasmodium falciparum, the most lethal of the human malariaparasites, but also integrate results from simian, avian and rodent models of malariathat were a major focus of early investigations into plasmodial metabolism.

http://www.malarianexus.com/articles/read/122/central-carbon-metabolism-of-plasmodium-parasites/

MALARIA: Artesunate versus quinine in the treatment of severe falciparum malaria in African children

Arjen M Dondorp et al.
Summary
Background
Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in African children with severe malaria.

Methods
This open-label, randomised trial was undertaken in 11 centres in nine African countries. Children (<15 years) with severe falciparum malaria were randomly assigned to parenteral artesunate or parenteral quinine. Randomisation was in blocks of 20, with study numbers corresponding to treatment allocations kept inside opaque sealed paper envelopes. The trial was open label at each site, and none of the investigators or trialists, apart from for the trial statistician, had access to the summaries of treatment allocations. The primary outcome measure was in-hospital mortality, analysed by intention to treat. This trial is registered, number ISRCTN50258054.

Findings
5425 children were enrolled; 2712 were assigned to artesunate and 2713 to quinine. All patients were analysed for the primary outcome. 230 (8·5%) patients assigned to artesunate treatment died compared with  297 (10·9%) assigned to quinine treatment (odds ratio [OR] stratifi ed for study site 0·75, 95% CI 0·63–0·90; relative reduction 22·5%, 95% CI 8·1–36·9; p=0·0022). Incidence of neurological sequelae did not diff er signifi cantly between groups, but the development of coma (65/1832 [3·5%] with artesunate vs 91/1768 [5·1%] with quinine; OR 0·69 95% CI 0·49–0·95; p=0·0231), convulsions (224/2712 [8·3%] vs 273/2713 [10·1%]; OR 0·80, 0·66–0·97; p=0·0199), and deterioration of the coma score (166/2712 [6·1%] vs 208/2713 [7·7%]; OR 0·78, 0·64–0·97; p=0·0245) were all signifi cantly less frequent in artesunate recipients than in quinine recipients. Post-treatment hypoglycaemia was also less frequent in patients assigned to artesunate than in those assigned to quinine (48/2712 [1·8%] vs 75/2713 [2·8%]; OR 0·63, 0·43–0·91; p=0·0134). Artesunate was well tolerated, with no serious drug-related adverse eff ects.

Interpretation:
Artesunate substantially reduces mortality in African children with severe malaria. These data, together with a meta-analysis of all trials comparing artesunate and quinine, strongly suggest that parenteral artesunate should replace quinine as the treatment of choice for severe falciparum malaria worldwide.

http://www.malarianexus.com/articles/read/116/artesunate-versus-quinine-in-the-treatment-of-severe-falciparum-malaria-in-african-children-aquamat-an-open-label-randomised-trial/

MALARIA: Malaria Parasite Caught Red-Handed Invading Blood Cells

ScienceDaily (Jan. 19, 2011) — Australian scientists using new image and cell technologies have for the first time caught malaria parasites in the act of invading red blood cells. The researchers, from the Walter and Eliza Hall Institute in Melbourne, Australia, and the University of Technology, Sydney (UTS), achieved this long-held aim using a combination of electron, light and super resolution microscopy, a technology platform new to Australia.

This image is a composite showing the behavior of different parts of the malaria parasite as it invades a red blood cell, at nanometer scales. The three components of the malaria parasite are labeled with fluorescent proteins (blue = parasite nucleus, red = secretory organelle, green = tight junction). The red blood cell is superimposed on the image for context. Image 1 (Attachment): The parasite is about to invade the red blood cell (unseen to the right of the picture). The tight junction (green) is like a window that the parasite brings with it and inserts into the red blood cell to gain entry. Image 2 (Invasion): This image is mid-invasion, the first time this step has even been visualized. The parasite "opens" the window it has inserted into the cell, and walks through. The secretory organelle (red) secretes its contents through the tight junction (green) and creates a vacuole which the parasite lives within in the red blood cell. In this image we see the parasite nucleus (blue) moving through the ‘window’ into the cell. Image 3 (Sealing): The parasite has completed invasion and is within a vacuole inside the host red blood cell. The window has been closed again, and will break down at a later stage. The parasite is now enclosed within its vacuole (red), the nucleus (blue) showing the parasite safely inside. (Credit: David Riglar and Jacob Baum (Walter and Eliza Hall Institute) with support from Cynthia Whitchurch and Lynne Turnbull (University of Technology, Sydney).)

The detailed look at what occurs as the parasite burrows through the walls of red blood cells provides new insights into the molecular and cellular events that drive cell invasion and may pave the way for developing new treatments for malaria. Institute researchers Dr Jake Baum, Mr David Riglar, Dr Dave Richard and colleagues from the institute's Infection and Immunity division led the research with colleagues from the i3 institute at UTS.
Dr Baum said the real breakthrough for the research team had been the ability to capture high-resolution images of the parasite at each and every stage of invasion, and to do so reliably and repeatedly. Their findings are published in today's issue of the journal Cell Host & Microbe.
"It is the first time we've been able to actually visualise this process in all its molecular glory, combining new advances developed at the institute for isolating viable parasites with innovative imaging technologies," Dr Baum said.

"Super resolution microscopy has opened up a new realm of understanding into how malaria parasites actually invade the human red blood cell. Whilst we have observed this miniature parasite drive its way into the cell before, the beauty of the new imaging technology is that it provides a quantum leap in the amount of detail we can see, revealing key molecular and cellular events required for each stage of the invasion process."
The imaging technology, called OMX 3D SIM super resolution microscopy, is a powerful new 3D tool that captures cellular processes unfolding at nanometer scales. The team worked closely with Associate Professor Cynthia Whitchurch and Dr Lynne Turnbull from the i3 institute at UTS to capture these images.
"This is just the beginning of an exciting new era of discoveries enabled by this technology that will lead to a better understanding of how microbes such as malaria, bacteria and viruses cause infectious disease," Associate Professor Whitchurch said.
Dr Baum said the methodology would be integral to the development of new malaria drugs and vaccines. "If, for example, you wanted to test a particular drug or vaccine, or investigate how a particular human antibody works to protect you from malaria, this imaging approach now gives us a window to see the actual effects that each reagent or antibody has on the precise steps of invasion," he said.
Malaria is caused by the Plasmodium parasite, which is transmitted by the bite of infected mosquitoes. Each year more than 400 million people contract malaria, and as many as a million, mostly children, die.
"Historically it has been very difficult to both isolate live and viable parasites for infection of red blood cells and to employ imaging technologies sensitive enough to capture snapshots of the invasion process with these parasites, which are only one micron (one millionth of a metre) in diameter," Dr Baum said.
He said one of the most interesting discoveries the imaging approach revealed was that once the parasite has attached to the red blood cell and formed a tight bond with the cell, a master switch for invasion is initiated and invasion will continue unabated without any further checkpoints.
"The parasite actually inserts its own window into the cell, which it then opens and uses to walk into the cell, which is quite extraordinary," Dr Baum said. "Visually tracking the invasion of Plasmodium falciparum into a red blood cell is something I've been aiming at ever since I began at the Walter and Eliza Hall Institute in 2003; it's really thrilling to have reached that goal. This technology enables us to look at individual proteins that we always knew were involved in invasion, but we never knew what they did or where they were, and that, we believe, is a real leap for malaria researchers worldwide."
This work was supported by the National Health and Medical Research Council, The University of Melbourne, Canadian Institutes of Health, the University of Technology, Sydney, and the Australian Research Council.
http://www.sciencedaily.com/releases/2011/01/110119125308.htm

MALARIA: risk warning to last-minute holidaymakers

18 January 2011

 Malaria falciparum, transmitted by this type of mosquito, can prove fatal if left untreated

 

Travel websites offering late deals to destinations where malaria is a risk should carry clear warnings, say experts.The call comes from doctors who had to treat three patients in a week, all of them UK citizens who had returned from "winter sun" holidays to The Gambia.All three patients, in their 40s and 50s, had booked their holidays with the same travel website. None had sought proper medical advice before travelling. If they had, they would have been told that malaria is endemic in the Western African country they were travelling to and advised of the need to take appropriate precautions.

Simple measures like covering up the skin by wearing long-sleeved shirts and trousers and using insect repellent, as well as taking malaria prevention tablets, can help avoid infection with the parasite that causes the disease that is transmitted by mosquito bites.
The three patients that the doctors at the James Cook University Hospital in Middlesbrough treated all had the most serious form of malaria - falciparum malaria.
One of the doctors, John Widdrington, said in a letter to the British Medical Journal: "Many travel websites and holiday brochures, including the website used by our patients, make no specific reference to the risk of contracting malaria.
"Travel websites need to include explicit messages about taking medical advice and effective chemoprophylaxis before travelling to malaria endemic areas.
"We've now written to the UK travel trade association Abta to flag this up to them."
He said part of the problem was people leaving the planning of their holidays until the last minute.
"The time to think about what health precautions you may need to take is before you book."
Some malaria tablets need to be taken for a couple of weeks before travelling to an affected area, for example.
"And as well as doing your own research about the area you will be travelling to, make sure you leave yourself enough time to see a doctor, either your own GP or one at a travel clinic, for advice," he said.
A spokeswoman from Abta said most travel websites did carry information about the risks of malaria, but that this was not always "upfront".
She said there was also an onus on the consumer to check properly for advice.
"When people are in a hurry not everybody will look in true depth and do all the research they need to.
"We recommend travellers follow Foreign Office advice," she said.
http://www.bbc.co.uk/news/health-12216682

MALARIA: Malaria vaccine hailed as a succes

Stephen Adams, 14 Jan 2011
A vaccine that almost halves the chance of catching malaria has the potential to save hundreds of thousands of lives a year, say scientists.
Research published online in The Lancet Infectious Diseases indicates that the vaccine reduces the risk of infection by the parasite that causes severe malaria by 46 per cent over 15 months.
Malaria, which is passed to humans via infected mosquitoes, is one of the biggest killers of children in Africa.
Of the 900,000 people killed by the disease across the continent every year, the majority are children under five.
While the vaccine does not give near total protection, as those for other diseases marketed for use in Western countries typically do, it still has the potential to save large numbers of lives.
In the phase II clinical trial, 447 children from Kenya and Tanzania, aged five to 17 months, were given the RTS,S/AS01E vaccine, while the same number were given the rabies vaccine as a 'control' group.
After 15 months, those who had the malaria vaccine were 46 per cent less likely to have been infected with the P Falciparum parasite than the control group. Only 11.4 per cent of those given the vaccine developed clinical malaria, compared to 19.7 per cent of the other group.
Dr Ally Olotu from the Kenya Medical Research Institute-Wellcome Trust Research Programme, who led the study, and fellow authors, concluded that the vaccine provides "sustained efficacy for at least 15 months and shows promise as a potential public health intervention against childhood malaria in malaria endemic countries".
The vaccine works by attacking the parasite when it first enters the bloodstream or liver cells, with the aim of completely preventing infection of red blood cells.
In 2008 results of a small-scale preliminary trial showed that it gave protection to 53 per cent of those vaccinated after eight months. However, the new study is larger, and shows only a small drop in the protection given after a further seven months.
The authors said more work was needed to see how well it worked in HIV-positive and malnourished children.
P falciparum is one of four species of malaria parasite that affect humans. It is found globally but is most common in Africa. It is the only one of the four species that can cause life-threatening malaria, according to the Wellcome Trust.
http://www.telegraph.co.uk/health/healthnews/8257496/Malaria-vaccine-hailed-as-a-success.html

MALARIA: Comparing two artesunate-based combination treatments on Plasmodium falciparum malaria

An open randomized clinical trial in comparing two artesunate-based combination treatments on Plasmodium falciparum malaria in Nigerian children: artesunate/sulphamethoxypyrazine/pyrimethamine (fixed dose over 24 hours) versus artesunate/amodiaquine (fixed dose over 48 hours)
Idowu Adejumoke Ayede, et al., Malaria Journal 2010, 9:378Background

Several studies have demonstrated the efficacy of artemisinin-combination therapy (ACT) across malaria zones of the world. Fixed dose ACT with shorter courses and fewer tablets may be key determinants to ease of administration and compliance.
Methods
Children aged one year to 13 years presenting with uncomplicated Plasmodium falciparum malaria were recruited in Ibadan, south-western Nigeria. A total of 250 children each were randomly assigned to receive three doses of artesunate/sulphamethoxypyrazine/pyrimethamine (AS + SMP) (12 hourly doses over 24 hours) or three doses of artesunate/amodiaquine (AS + AQ) (daily doses over 48 hours). Efficacy and safety of the two drugs were assessed using a 28-day follow-up and the primary outcome was PCR- corrected parasitological cure rate and clinical response.

Results
There were two (0.4%) early treatment failures, one in each treatment arm. The PCR corrected cure rates for day 28 was 97.9% in the AS + AQ arm and 95.6% in the As + SMP arm (p = 0.15). The re-infection rate was 1.7% in the AS + AQ arm and 5.7% in the AS + SMP arm (p=0.021). The fever clearance time was similar in the two treatment groups: 1 - 2 days for both AS + SMP and AS + AQ (p = 0.271). The parasite clearance time was also similar in the two treatment groups with 1- 7 days for AS + SMP and 1- 4 days for AS + AQ (p = 0.941.). The proportion of children with gametocytes over the follow-up period were similar in both treatment groups. Serious Adverse Events were not reported in any of the patients and in all children, laboratory values (packed cell volume, liver enzymes, bilirubin) remained within normal levels during the follow-up period but the packed cell volume was significantly lower in the AS/ SMP group.
Conclusions
This study demonstrates that AS + SMP FDC given as three doses over 24 hours (12-hour intervals) has similar efficacy as AS + AQ FDC given as three doses over 48 hours (24-hour interval) for the treatment of uncomplicated Plasmodium falciparum malaria in children in Nigeria. Both drugs also proved to be safe. Therefore, AS+SMP could be an alternative to currently recommended first-line ACT with continuous resistance surveillance
http://www.malariajournal.com/content/9/1/378