Malaria evades the Human Body's Immune system

It’s known that malaria causes a highly inflammatory response in infected individuals that leads to the deadly clinical complications of anemia and cerebral disease.

The Yale research team learned that the parasites produce their own version of a human cytokine, or immune hormone, which directs the inflammatory response during malaria.

They also discovered that this cytokine, called PMIF, incapacitates the anti-malaria, memory T-cell immune response.

Using a genetically modified strain of the malaria parasite in mice, the Yale team found that PMIF causes host T-cells to develop into short-lived effector cells rather than protective memory cells.

The short-lived cells die during the infection, and the long-lived memory T-cells are not produced in adequate numbers to combat the infection or to protect from re-infection, which occurs repeatedly in malaria-endemic regions.

“These findings indicate that malaria parasites actively interfere with the development of immunological memory, and may account for the inhibition of protective immune responses in human malaria,” said Rick Bucala, M.D., professor of internal medicine, pathology, and epidemiology and public health at Yale School of Medicine.

• “This knowledge will help us identify specific therapies that can protect anti-malarial T-cells from death and improve an individual’s immune response to infection or to vaccination.”

More information: PNAS paper: www.pnas.org/conte… ull.pdf+html

Malaria: Prevention by Blocking Cell’s Passage

Researchers at the Wellcome Trust Sanger Institute have discovered an understanding on how the most deadly species of malaria parasite, Plasmodium falciparum, invades human red blood cells.

They used the technique called Avidity-based Extracellular Interaction Screen (AVEXIS), which discovered the interaction between the parasite protein and the host receptor.

The parasite relies on a single receptor on the red blood cell's surface to invade, offering an exciting new focus for vaccine development.

The blood stage of Plasmodium's lifecycle begins when the parasite invades human red blood cells, and it is this stage that is responsible for the symptoms and mortality associated with malaria.

"Our research seems to have revealed an Achilles' heel in the way the parasite invades our red blood cells. It is rewarding to see how our techniques can be used to answer important biological problems and lay the foundations for new therapies," senior co-author Gavin Wright said in a statement.

However, researchers demonstrated that disrupting this interaction completely blocked the parasite from gaining entry into the red blood cell. Importantly, this was true across all parasite strains tested, making it appear that the receptor is a universal entry pathway. It is hoped that the parasite's dependency on this one protein can now be exploited to develop new and effective vaccines.

Malaria kills approximately one million people every year, mostly children under the age of five in sub-Saharan Africa. Researchers have tried for many years to develop a vaccine to prevent the parasite gaining entry into our red blood cells, but so far they have been unsuccessful.

One of the challenges is that the parasite is adaptable - although several red blood cell receptors had been previously identified, none was shown to be essential: when entry through one receptor is prevented, the parasite is able to switch to another. This new research has found a single receptor that is absolutely required by the parasite to invade.

"The discovery of a single receptor that can be targeted to stop the parasite infecting red blood cells offers the hope of a far more effective solution," Investigator at the Jenner Institute, Adrian Hill, said.

According to the Health Protection Agency, malaria is not endemic in the UK, but in the five years between 2006 and 2010, almost 1600 cases have occurred every year on average in travellers returning to or arriving in the UK from malaria-endemic countries.

Fighting Malaria: Venderbilt and Yale Scientists Transplant the Nose of Mosquito

Scientists at Vanderbilt and Yale universities have successfully transplanted most of the "nose" of the mosquito that spreads malaria into frog eggs and fruit flies and are employing these surrogates to combat the spread of the deadly and debilitating disease that afflicts 500 million people.

The research is described in two complimentary papers, one published this week in the early online edition of the Proceedings of the National Academy of Sciences and the other which appeared online Feb. 3 in the journal Nature.

The mosquito's "nose" is centered in its antennae, which are filled with nerve cells covered with special "odorant receptors" that react to different chemical compounds. The insect ORs are comparable to analogous receptors in the human nose and taste buds on the tongue.

"We've successfully expressed about 80 percent of the Anopheles mosquito's odorant receptors in frog's eggs and in the fruit fly antennae," says Laurence Zwiebel, professor of biological sciences at Vanderbilt, whose lab performed the frog egg transplantation. The fruit-fly (Drosophila melanogaster) work was done in the laboratory of John Carlson, Eugene Higgins Professor of Molecular, Cellular and Developmental Biology at Yale.

Both accomplishments are part of a five-year project supported by the Grand Challenges in Global Health Initiative funded by the Foundation for NIH through a grant from the Bill and Melinda Gates Foundation with the goal of producing novel ways to inhibit the spread of malaria. Scientists from the Wageningen University in the Netherlands, the African Insect Science for Food and Health Institute in Kenya, Ifakara Health Institute in Tanzania and the Medical Research Council Laboratories in the Gambia are also participating in the project.

Mosquito borne infection of Dengue Fever reaching Epidemic proportions in Philipines

A government worker fumigates a slum community in Manila in an attempt to control the spread of dengue fever.

Mosquito: The Human World's Deadliest Enemy

AP/PA Photos

The mosquito rarely lives longer than a month and is not as ferocious or visually intimidating as a raging carnivore, but it comes in much more regular and intimate contact with humans, than any other dangerous creature. It also rapidly spreads deadly and contagious diseases, leading to the death of more humans, than any other member of the animal kingdom. By injecting parasites and viruses into the blood stream, the mosquito causes upwards of two million deaths a year. According to Dr. Mark Rowland of the London School of Hygiene and Tropical Medicine, malaria is responsible for 800,000 to one million of those deaths. Malaria, Elephantiasis, West Nile virus, dengue fever, yellow fever, etc are all deadly diseases that are spread by mosquitoesand there are many more. While the most dangerous breeds of the bug are local to Africa, Asia and North America, it’s still a good idea to stock up on bug repellent for those humid, mosquito-filled nights.

Malaria and Dengue on the Run

Aedes aegypti. The head is at centre right, with large compound eyes (blue). There are two hairy antennae and a long proboscis (pink) used for penetrating human skin and sucking blood (Image: Eye Of Science / SPL)" title="A coloured scanning electron micrograph (SEM) of the head of a female yellow fever mosquito, Aedes aegypti. The head is at centre right, with large compound eyes (blue). There are two hairy antennae and a long proboscis (pink) used for penetrating human skin and sucking blood (Image: Eye Of Science / SPL)">

A coloured scanning electron micrograph (SEM) of the head of a female yellow fever mosquito, Aedes aegypti. The head is at centre right, with large compound eyes (blue). There are two hairy antennae and a long proboscis (pink) used for penetrating human skin and sucking blood (Image: Eye Of Science / SPL)

Female A. aegypti feed almost exclusively on human blood (see image), and unlike most other mosquito species, it thrives in human habitats. Their larvae grow readily in water-filled plant pot plates and discarded plastic containers. Some even claim that it is more adept at avoiding well-aimed swats.

When an A. aegypti mosquito (see image) bites someone who has dengue, the virus begins replicating in the mosquito's gut. From there it spreads to the salivary gland and, 10 to 14 days after being infected, the mosquito's saliva contains enough virus to infect anyone it bites.

The aim is to combat dengue fever, a mosquito-borne disease that has reached pandemic proportions in a matter of decades. If the new approach works against dengue fever it should also work against other insect-borne diseases, including the biggest killer, malaria. That possibility has won the team developing this strategy funding through the Bill and Melinda Gates Foundation.

The potential benefits are huge, but before it can go ahead the team will have to convince people the strategy is safe. If things go wrong, it might make dengue spread even faster.

Still, the situation is already pretty bad. In south-east Asia, long plagued by dengue, outbreaks are becoming bigger, more frequent and longer lasting. In Australia, the Pacific and most of the Americas, where dengue was once rare, the disease is taking hold with a vengeance. An outbreak earlier this year that affected at least 60,000 people in Brazil and Argentina reached Buenos Aires for the first time.