Malaria in Africa

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QUESTION

How many in Africa have been affected by Malaria?

ANSWER

In 2010, there were approximately 174 million cases of malaria in Africa. However, some people may present with more than one case of malaria per year (especially young children), so the number of people affected is likely considerably lower. However, 90% of deaths from malaria occur in Africa, and 60% in just six countries: Nigeria, DR Congo, Burkina Faso, Mozambique, Cote d’Ivoire and Mali. The good news is that malaria mortality has dropped by 33% in Africa since 2000, which is a very encouraging trend, though the aim of organizations such as Malaria No More is to fully eliminate deaths from malaria globally by 2015.

Researchers Cure Mice of Bloodstream Malaria Infection

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Researchers have discovered how malaria manipulates the immune system to allow the parasite to persist in the bloodstream. By rescuing this immune system pathway, the research team was able to cure mice of bloodstream malaria infections.

The findings could point the way to a new approach for treating malaria that does not rely on vaccination and is not susceptible to the parasite’s notorious ability to develop drug resistance.

“Malaria is chronic, prolonged infection and the host immune defense has a tough time clearing it and sometimes it never clears it,” says Noah Butler, Ph.D., UI postdoctoral research scholar at the University of Iowa,  and lead study author. “We’ve determined that this prolonged infection actually drives dysfunction of the immune cells that are supposed to be fighting the infection, which in essence allows further persistence of the parasite infection.”

More specifically, the study showed that the malaria parasite stimulate these key immune cells (known as CD4+ T cells) so that they continuously express molecules called inhibitory receptors. Under normal circumstances, these molecules help to “apply the brakes” to the immune response and prevent over-activation that can be harmful. However, by keeping the mechanism turned on, the malaria parasite damps down the immune response significantly, reducing the T cells’ ability to fight the parasite and allowing it to persist.

Importantly, the team also showed that blocking the action of the inhibitory receptor molecules resulted in immediate and complete clearance of the malaria parasite.

“When we blocked the function of these molecules, we took the brakes off the host’s immune response and everything got better — the overall immune response was dramatically improved and there was immediate control and accelerated clearance of the parasite,” says John Harty, Ph.D., professor of microbiology and pathology at the UI Carver College of Medicine and senior study author. “These findings suggest an alternative approach for the treatment of existing malaria infection.”

200 million malaria cases

More than half the world’s population is at risk of malaria, a mosquito-borne parasite that causes anemia and high fever and which can persist for weeks or months. There are more than 200 million cases of malaria each year and an estimated 800,000 children die from malaria annually.

Harty notes that the current study was done in mice and it is not yet known if the same approach will work in humans. However, two factors suggest the strategy may have potential. First, drugs that block inhibitory receptor molecules are available and currently being tested as cancer therapies. And second, the UI team found that malaria infection in humans does lead to increased expression of inhibitory receptors on CD4+ T cells suggesting that these molecules could represent a viable target for human therapies.

The human findings were the product of an important collaboration between the UI team and malaria researchers working in the sub-Saharan country of Mali. The Mali team based at the University of Bamako works in a sophisticated lab set up by the National Institutes of Health. In Mali’s dry season there are no mosquitoes, so there’s no malaria; in the wet season, the mosquitoes come out and malaria appears.

“Workers in the NIH lab obtained blood samples from malaria-free children at the end of the dry season, and then when some of the children returned to the clinic with malaria at the beginning of the next wet season they were treated immediately and the workers also took a second blood sample,” Harty explains. “This allowed us to analyze the blood for expression of this inhibitory molecule before and after infection and we found that the molecule went up after infection.”

Malaria further compromises immune system

A second collaboration, born closer to home, allowed Harty’s team to prove that it is the CD4+ T cells that are disrupted by the malaria infection.

Using a new technique that was developed in the lab of UI microbiologist Steve Varga, Ph.D., the researchers were able to track the behavior of the responding T cells during malaria infection. They found that chronic malaria infection led to sustained expression of the inhibitory receptor molecules on the surfaces of this type of T cell and also showed that the T cells’ ability to fight the parasite was significantly reduced.

The study also found that as the parasite persists the inhibitory receptor molecules remain upregulated and the immune system became more and more compromised.

“The T-cells are so over-stimulated that they eventually lose their function or even die — this is known as T-cell exhaustion,” Butler explains.

The concept that prolonged persistence of an “insult” to the immune system, such as cancer or chronic viral infections like HIV, disrupts and exhausts the immune response is well established. However, this study is the first time it has been shown for malaria. The study finding suggests that rescuing CD4+ T cells from exhaustion could be an effective strategy to control and clear bloodstream malaria infections.

The study was undertaken by University of Iowa researchers and colleagues, and was published Dec. 11, 2011 in the Advance Online Publication of the journal Nature Immunology.  In addition to Harty and Butler, UI researchers Lecia Pewe, Lorraine Tygrett, and Thomas Waldschmidt, Ph.D., also were involved in the study. The team also included Jacqueline Moebius and Peter Crompton from the National Institute of Allergy and Infectious Diseases in Rockville, Md., and Boubacar Traore and Ogobara Doumbo from the Malaria Research and Training Center, University of Bamako in Mali.

The study was funded in part by grants from the NIH and the UI Department of Microbiology.

Source: University of Iowa Health Care Media Relations, 200 Hawkins Drive, Room W319 GH, Iowa City, Iowa 52242-1009

Global Fund Responds to News Stories About Corruption in Grant Spending

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Officials from the Global Fund to Fight AIDS, Tuberculosis and Malaria are criticizing recent media reports of misuse of Global Fund grants. They say the reports are based on incidents that occurred and were acted on last year and contain no new revelations.

The media reports claim corruption is taking a big bite out of the billions of dollars of grant money disbursed by the Global Fund. And, they contend as much as two-thirds of some grants are used fraudulently.

The Fund’s Executive Director, Michel Kazatchkine, says the Global Fund has zero tolerance for corruption and actively seeks to uncover any evidence of misuse of its funds.

He says the incidents referred to in recent media reports concern the grave misuse of funds in four of the 145 countries that receive grants. He says those cases figured prominently in last year’s Inspector General’s report.

“As a result, immediate steps were taken in Djibouti, in Mali, in Mauritania and in Zambia, to recover misappropriated funds and to prevent future misuse of grant money,” he said. “In total, the Global Fund is demanding the recovery of $34 million unaccounted for in these and other countries out of a total disbursement of $13 billion.”

Kazatchkine says criminal proceedings are underway in Mali, Mauritania and Zambia. He says the Fund has suspended relevant grants in Mali and Zambia and ended another grant in Mali.

Kazatchkine says transparency is a fundamental principle behind all of the work of his organization. He adds the Global Fund is fully accountable to its donors about all of its expenditures and is committed to preventing any misuse of its money.

”What is of concern to me, of course, is that this shakes beyond that a global public opinion somehow at a time when governments are under pressure to cut public expenditures and where millions of lives that depend on the Global Fund and the hope the Global Fund is bringing to the world could thus be at risk,” said Kazatchkine.

Kazatchkine says the lives of 4,000 people suffering from AIDS, tuberculosis and malaria are saved every day as a consequence of the grant money disbursed by the Fund.

He says the Fund and the Office of the Inspector General are strengthening efforts to prevent fraud. He says so-called higher risk countries are being closely monitored to make sure none of the money goes astray.

Source: VOA