Malaria Against Malaria: A Pre-Existing Malaria Infection Can Prevent a Second Infection,

Malaria Against Malaria: A Pre-Existing Malaria Infection Can Prevent a Second Infection, Study Suggests


ScienceDaily (May 15, 2011) — A team of researchers have found that pre-existing malaria prevents secondary infection by another Plasmodium strain, the parasite responsible for malaria, by restricting iron availability in the liver of the host. This discovery was published on May 15 in Nature Medicine and has important implications for the management and prevention of malaria, a condition which affects millions of individuals worldwide.
The study was developed by the team led by researcher Maria M. Mota at Instituto de Medicina Molecular in Lisbon, Portugal, in collaboration with researchers at the Weatherall Institute of Molecular Medicine and Oxford University; and was funded by the Portuguese Fundação para a Ciência e Tecnologia, European Science Foundation and Medical Research Council, UK.
In this current study, the researchers focused at how malaria parasites developed in both the liver and in red blood cells and analysed patterns of infection in mice, looking in particular at cases of 'superinfection', in which an individual already infected with malaria is later bitten by a second infected mosquito. An individual in a high risk area can be bitten by hundreds of malaria-infected mosquitoes per year, making the issue of superinfection highly relevant. The study reveals for the first time the crucial role of iron in the development of multiple malarial infections, which has strong implications for iron supplementation used to combat anaemia in malaria-endemic regions.
After a mosquito bite, malaria parasites first travel to the liver, multiply, then escape and invade red blood cells. It was previously understood that parasites in both the liver and in blood need iron in order to grow. This new study shows that a second mosquito bite of an individual, already carrying blood parasites, does not lead to a full-blown second infection. The superinfection is blocked in the liver by the first infection. This protective effect is due to the blood parasites causing the parasites in the liver to be starved of iron, so that they cannot grow. In that respect, the results challenge the biological concept that infection of distinct host cells (liver hepatocytes or red blood cells) occur independently from each other, which may also have impact in the research area of infection (beyond malaria).
Dr Silvia Portugal, first author of the study says: "I am very happy that we were able to find such an interesting interaction occurring between different malaria parasite stages in a single host, and that this might contribute for future control of malaria."
Dr Maria Mota, who led the study at Instituto de Medicina Molecular in Lisbon says: "Our findings help explaining the differences in infection risk and complexity of infections in young individuals observed in endemic-malaria regions that have hitherto required speculative explanations. Also, they challenge the idea that infection in distinct cell types is independent, which may have an impact in future research in the field of infectious diseases as a whole. "
Dr Hal Drakesmith who co-led the study at the Weatherall Institute of Molecular Medicine adds: "'Now that we understand how malaria parasites protect their territory in the body from competitor parasites, we may be able to enhance this natural defence mechanism to combat the risk of malaria infections. At the same time we may need to look again at the advisability of iron supplementation programmes in malaria-endemic regions, as possible increased risk of infection may need to be weighed against benefits -- more data is needed on this issue."
Malaria is a devastating disease that affects extensive areas of Africa, Asia, South and Central America, causing several thousands of deaths per year in children under the age of five. Malaria is caused by the infection of the protozoan parasite Plasmodium, which belongs to the phylum Apicomplexa. Attempts to eradicate malaria have so far been unsuccessful. Their failure can be attributed to increasing resistance to insecticides in the mosquito vector and to anti-malarial drugs in the parasite. There is an urgent need of developing novel strategies against malaria.
http://www.sciencedaily.com/releases/2011/05/110515145805.htm

Parasites' struggle for survival 'makes malaria deadly'

14 February 2011

 Malaria - spread by mosquitoes - kills one million people every year

Edinburgh University scientists have claimed malaria is particularly deadly because the parasites which carry it battle other infections for survival.
They found, when malaria parasites enter the bloodstream, they alter their plan of attack if they face competition from other strains of the infection.
However, it means they have less resources left to spread the disease.
Malaria, which is spread by mosquitoes, kills about one million people every year.
The scientists found the malaria parasites focus on producing cells that replicate quickly to cause infection, rather than cells capable of being taken up by a feeding mosquito and spreading the disease.
Since malaria infections usually consist of multiple, competing strains of the parasite, this attack strategy is the best way to beat the competition, the scientists said.
However, it means the parasites pay a high price, as they therefore have fewer resources left to spread the disease.

'Fight it out'
Laura Pollitt of Edinburgh University's school of biological sciences said: "Our results explain a long-standing puzzle of parasite behaviour. "We found that when parasites compete with each other, they respond with a sophisticated strategy to safeguard their long-term survival. They opt to fight it out in the bloodstream rather than risk everything on the chance of infecting mosquitoes in the short term."
The research, published in the American Naturalist, was funded by the Wellcome Trust, the Biotechnology and Biological Sciences Research Council and the Natural Environment Research Council.
http://www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-12448466

MALARIA: Evolutionary forces on Anopheles: what makes a malaria vector?

Cohuet, A., et al.Institut de Recherche pour le Développement, Montpellier, France
In human malaria, transmission intensity is highly dependent on the vectorial capacity and competence of local mosquitoes. Most mosquitoes are dead ends for the parasite, and only limited ranges of Anopheles are able to transmit Plasmodium to humans. Research to understand the determinants of vectorial capacity and competence has greatly progressed in recent years; however, some aspects have been overlooked and the evolutionary pressures that affect them often neglected. Here, we review key factors of vectorial capacity and competence in Anopheles, with a particular focus on the most important malaria vector Anopheles gambiae. We aim to point out selection pressures exerted by Plasmodium on Anopheles to improve its own transmission and discuss how the parasite might shape the vector to its benefit. © 2009 Elsevier Ltd. All rights reserved.
http://www.scopus.com/record/display.url?eid=2-s2.0-77049109244&origin=inward&txGid=F43pX9mfrGMCwIyvjybA0R1%3a12

MALARIA: Can We Simplify Malaria History?

Scientific American is known for making the latest scientific advances - from dark matter to disease management - accessible to a wide audience. An article in the November 2010 issue on malaria vaccine progress is generally a good example. The following passage though, may simplify the history of eradication a bit too much.
In the 1960s an enormous campaign wiped out the disease in many parts of the world and drove down its number in others. But that success ultimately bred its own end. As malaria became perceived as less of a threat, global health agencies became complacent; their chief tool, DDT, was found to be toxic to birds, and they largely abandoned their efforts. Malaria numbers roared back more fiercely than before.
Two specific issues from the foregoing do not paint the full picture. First, bird deaths did not stop malaria eradication, though the toxicity issue is true in its own context. The real end of DDT was bred by mosquitoes developing resistance to the pesticide, which was discerned even before the campaign reached its height. The Lancet in reviewing Randal Packard’s book, The Making of a Tropical Disease, a Short History of Malaria, explained that …It (the eradication campaign)was far too monodimensional, relied too much on DDT spraying, and neglected the palpable problem that the delivery infrastructure was not in place in too many parts of the malarious world. The emergence of widespread mosquito resistance to DDT, and parasite resistance to the cheap mainstay of therapy, chloroquine, compounded the difficulties.

Secondly, at least for colleagues in the US Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO), malaria research overall did not halt. Surely the funding levels were not as high as we see today, but persistent research provided us with new tools including insecticide treated bednets, artemisinin-based combination therapy, and nearly a dozen insecticides for indoor residual spraying, for which we are thankful.
True, these additional tools do not confer permanent immunity as a vaccine eventually should, but their implementation has driven down the number of malaria deaths in many countries, and when a vaccine comes along to strengthen the toolkit, we will be farther down the long road to elimination. The malaria lifecycle is complex, and health systems designed to deliver malaria interventions is equally complex (and challenging), which means we cannot and should not expect a magic bullet in the near future.
As Randal Packard pointed out a key lesson from the first eradication campaign needs repetition, lest we again blame it all on the birds. Aside from developing insecticide resistance, there was clear indication that the health systems in the most highly endemic areas were not able to maintain continuous IRS application.
Health systems are stronger today, due in part to recognition by partners (international and internal) that malaria cannot be controlled, much less eliminated, without health system strengthening. It is these same health systems that will also be required to deliver the new malaria vaccines, so they better be strengthened before vaccines are rolled out.
Another short note of concern about the Scientific American article - in a box entitled “Plan B: Vaccine Alternatives” we are correctly shown that the effort to eliminate malaria has other tools that must be sustained. Unfortunately the text refers to malaria as a ‘virus’, though elsewhere in the article the stress on ‘parasite’ prevails.
http://www.malariafreefuture.org/blog/?p=1111

MALARIA: Wild Chimpanzees Infected with 5 Plasmodium Species

Data are missing on the diversity of Plasmodium spp. infecting apes that live in their natural habitat, with limited possibility of human-mosquito-ape exchange. We surveyed Plasmodium spp. diversity in wild chimpanzees living in an undisturbed tropical rainforest habitat and found 5 species: P. malariae, P. vivax, P. ovale, P. reichenowi, and P. gaboni.

Despite ongoing and, in some regions, escalating morbidity and mortality rates associated with malaria-causing parasites, the evolutionary epidemiology of Plasmodium spp. is not well characterized. Classical studies of the blood pathogens of primates have found protozoa resembling human malaria parasites in chimpanzees and gorillas; however, these studies were limited to microscopy, negating conclusions regarding evolutionary relationships between human and ape parasites. Recent studies that used molecular approaches showed that captive and wild chimpanzees (Pan troglodytes) and lowland gorillas (Gorilla gorilla), as well as captive bonobos (Pan paniscus), harbor parasites broadly related to P. falciparum; wild and captive gorillas and captive bonobos and chimpanzees are sometimes infected with P. falciparum itself. Further, captive chimpanzees and bonobos have been shown to have malaria parasites related to human P. ovale and P. malariae; P. vivax has been identified in various monkeys and 1 semiwild chimpanzee. Recently, P. knowlesi, a simian malaria species, became the fifth human-infecting species, highlighting the possibility of transmission of new Plasmodium spp. from wild primates to humans.

http://www.cdc.gov/eid/content/16/12/1956.htm

MALARIA: video of life cycle of plasmodium

Another great video of the plasmodium life cycle
Learning has never been so easy!

http://www.youtube.com/watch?v=iwAEsOpvHn0&feature=player_embedded

MALARIA: history of spread

When humans left Africa some 50,000 to 60,000 years ago, some were already infected with the world's most deadly malaria parasites, a new study says. The findings contradict the view, held by some scientists, that malaria only began afflicting us about 10,000 years ago, around the time agriculture was invented.
Transmitted by Anopheles mosquitoes, the Plasmodium falciparum parasite infects hundreds of millions of people every year and may kill more than a million. Researchers are still debating when this scourge first began afflicting us. Some have argued that a predecessor to the parasite must have infected the last common ancestor to humans and chimps, 6 million or 7 million years ago, and then co-evolved when Homo sapiens stepped onto the world stage in a process called cospeciation. In this scenario, a related species, P. reichenowi, co-evolved with chimpanzees.
But others, such as famed evolutionary biologist Francisco Ayala of the University of California, Irvine, argue that P. reichenowi jumped the species barrier from chimps to humans quite recently and then became P. falciparum. Ayala believes that this may have happened as recently as 10,000 years ago, when humans settled down and started farming; at that time, irrigation and huts would have created ideal breeding grounds for mosquitoes to help the parasites spread. Genetic studies allowing scientists to draw the Plasmodium family tree should be able to settle the issue, but so far, there's no consensus.
The new paper, published yesterday in Current Biology, doesn't quite solve the question of whether cospeciation occurred, but it claims that malaria couldn't possibly have arisen with the advent of agriculture. The authors, from 13 institutes on four continents, reasoned that if humans were suffering from malaria when they left the African continent, it should be evident in the genetic makeup of parasite populations in different parts of the world; the theory predicts that parasites farther away from Africa should be less diverse, just as is the case in humans.
So the team analyzed hundreds of malaria samples from seven countries, sequencing two genes to determine genetic variability within each local population, all the way from West Africa to Indonesia and Oceania. (The Americas, where malaria is believed to have been introduced just several hundred years ago during the slave trade, were left out of the main analysis.)
The researchers found that genetic diversity did indeed decrease at greater distances from Africa. The correlation is very strong, says lead author Francois Balloux of the MRC Centre for Outbreak Analysis and Modelling in London, and the pattern matches human migration out of Africa, which scientists believe started some 50,000 to 60,000 years ago.
"It makes sense," says Austin Hughes of the University of South Carolina, Columbia, who recently published another analysis showing that malaria has been with humans for a very long time. "It's consistent with everything we have tried to say for a long time."
http://news.sciencemag.org/sciencenow/2010/06/when-humans-left-africa-malaria-.html?etoc

MALARIA: plasmodium DNA evolution

Scientists have determined the evolutionary timeline for the microscopic parasites that cause one of the world's most widespread infectious diseases: malaria.
Having an understanding of the origins of the lineages of such pathogens, or disease-causing organisms, is fundamental to understanding emerging diseases, according to the researchers.The origin of malaria in humans has been dated to as recent as 10,000 years ago and as long as several million years ago.Now biologists Robert Ricklefs of the University of Missouri-St. Louis and Diana Outlaw of Mississippi State University in Starkville have found a molecular clock for malaria parasites that provides a more precise date.The results of their research, funded by the National Science Foundation (NSF), appear in this week's issue of the journal Science.The findings provide a well-supported time calibration for the evolution of malaria parasites.
By marrying DNA research with a new statistical approach, the biologists were able to get a better handle on the timeline of parasite evolution.The scientists found that a key gene in malaria parasites evolved at 60 percent of the rate of the same gene in its hosts.Knowing the rate of gene evolution of the vertebrate hosts, the biologists were able to estimate that modern malaria parasites began to diversify across mammals, birds and reptiles about 16 million years ago.The ancestors of humans acquired the parasite 2.5 million years ago."Malaria parasites undoubtedly were relatively benign for most of that history, becoming a major disease only after the origins of agriculture and dense human populations," said Ricklefs."These findings are important in providing a quantitative rate of evolution for malaria," said Alan Tessier, program director in NSF's Division of Environmental Biology, which funded the research."They also reveal that host-switching can result in a rapid diversification of parasites, and decouple their evolution from that of their hosts," Tessier said."Because single-celled malaria parasites leave no fossil record, one has to estimate their rate of evolution by comparison with their hosts," said Ricklefs."Previously, this had been done under the assumption that parasites evolve at the same rate as their hosts and thus were the same age as their hosts."Ricklefs and Outlaw's research suggests that the parasites may jump to new, unrelated hosts at any time."One cannot equate parasite evolution," said Ricklefs, "with a host's evolution."
http://www.infozine.com/news/stories/op/storiesShowPrinter/PrintId/42183/?goto=print