We estimate the protective efficacy of insecticide-treated mosquito nets and indoor-residual spraying on reducing malaria-attributable mortality 1–59 months to be 55%, with a range of 49–61%, in Plasmodium falciparum settings.
We estimate malaria prevention interventions in pregnancy (intermittent preventive therapy and insecticide-treated mosquito nets) to have a pooled protective efficacy of 35% (95% confidence interval: 23–45%) on reducing the prevalence of low birth weight in the first or second pregnancy in areas of stable Plasmodium falciparum transmission.
These data support the continued scale-up of these malaria prevention interventions in endemic settings that will prevent a considerable number of child deaths due directly and indirectly to malaria.
These protective efficacy estimates will allow the use of the LiST model for estimating the likely impact of past intervention scale-up, as well as for predicating future impact of intervention scale-up by national malaria control programs.
http://ije.oxfordjournals.org/cgi/content/full/39/suppl_1/i88?view=long&pmid=20348132
Showing posts with label Malaria prevention. Show all posts
Showing posts with label Malaria prevention. Show all posts
Saturday, 12 June 2010
Wednesday, 26 May 2010
MALARIA: Keeping the plasmodium in the red cell
Boston, MA -- Harvard School of Public Health (HSPH) researchers and colleagues seeking to block invasion of healthy red blood cells by malaria parasites have instead succeeded in locking the parasites within infected blood cells, potentially containing the disease.
The findings reveal an essential step in the biology of the most common and severe malaria parasite, Plasmodium falciparum, and offer a new drug target for fighting one of the world's most common and dangerous infections.
Malaria sickens up to one half billion people every year and kills up to one million, mostly children in sub-Saharan Africa. The high fevers, shaking chills, flu-like symptoms, and anemia can be fatal unless treated quickly. Malaria has grown resistant to a long list of drugs, and vaccines are still in experimental stages.
Working with the malaria parasite and human blood in test tubes and lab dishes, the research team identified a single fast-acting protein in the parasite that enables it and several dozen of its offspring to escape from a human red blood cell in preparation for quick invasion of many more healthy blood cells. Eliminating that protein traps the parasites in the cell.
After an infected mosquito bites a person, malaria parasites move into the liver, where they silently mature and multiply within weeks. Malaria parasites make people sick weeks or months later when they enter red blood cells and begin an exponential expansion. In a single cell, a parasite produces up to 32 offspring in about two days, which burst out to infect more red blood cells.
"This is the stage where things have to happen very fast for the parasite," said senior author Manoj Duraisingh, HSPH assistant professor of immunology and infectious diseases and senior author of the paper in the May 14 Science. "The parasite doesn't like to spend much time outside the cell. It grows and matures, and immediately following rupture, enters a new cell. It was a surprise that this protein kinase, which we thought would be involved in red blood cell invasion, turns out to be essential for the parasite getting out of the cell."
The study helps define the exit of the parasite from a blood cell as a highly choreographed process and distinguishes the egress and invasion steps, the researchers said.
"When the parasite gets out of the red blood cell, it has a matter of seconds or minutes to get into new red blood cells, or it will be cleared or killed by the human immune system," said first author Jeffrey Dvorin, a postdoctoral research fellow in the Duraisingh Lab at HSPH and a clinical fellow in pediatric infectious diseases at Children's Hospital Boston. "We found an important trigger for the parasite to exit cells that may be independent from the invasion trigger."
Even better, the protein is found in the parasite and in plants, but not in humans, which means a drug targeted to that protein may be less toxic for people. The protein belongs to a family of Plasmodium falciparum calcium-dependent protein kinases, or PfCDPK5 for short in this case. Other members of the family have been implicated in parasite egress of red blood cells, but this is the first study using a genetic technique to validate a protein critical for parasite egress of red blood cells, according to the researchers.
Many companies and labs are looking for inhibitors of parasite egress and invasion of red blood cells, but no anti-malarial drugs yet target these stages of the parasite lifecycle, Dvorin said.
The paper also demonstrates the usefulness of a new tool that can be used to evaluate additional members of the kinase family, as well as other signaling pathways that regulate key events in the blood stage of malaria infection. As of 2002, "we have a malaria genome of about 6,000 genes," said Duraisingh. "We need a means of prioritizing specific gene candidates for further drug development."
http://www.sciencecodex.com/new_twist_on_potential_malaria_drug_target_acts_by_trapping_parasites_in_cells
The findings reveal an essential step in the biology of the most common and severe malaria parasite, Plasmodium falciparum, and offer a new drug target for fighting one of the world's most common and dangerous infections.
Malaria sickens up to one half billion people every year and kills up to one million, mostly children in sub-Saharan Africa. The high fevers, shaking chills, flu-like symptoms, and anemia can be fatal unless treated quickly. Malaria has grown resistant to a long list of drugs, and vaccines are still in experimental stages.
Working with the malaria parasite and human blood in test tubes and lab dishes, the research team identified a single fast-acting protein in the parasite that enables it and several dozen of its offspring to escape from a human red blood cell in preparation for quick invasion of many more healthy blood cells. Eliminating that protein traps the parasites in the cell.
After an infected mosquito bites a person, malaria parasites move into the liver, where they silently mature and multiply within weeks. Malaria parasites make people sick weeks or months later when they enter red blood cells and begin an exponential expansion. In a single cell, a parasite produces up to 32 offspring in about two days, which burst out to infect more red blood cells.
"This is the stage where things have to happen very fast for the parasite," said senior author Manoj Duraisingh, HSPH assistant professor of immunology and infectious diseases and senior author of the paper in the May 14 Science. "The parasite doesn't like to spend much time outside the cell. It grows and matures, and immediately following rupture, enters a new cell. It was a surprise that this protein kinase, which we thought would be involved in red blood cell invasion, turns out to be essential for the parasite getting out of the cell."
The study helps define the exit of the parasite from a blood cell as a highly choreographed process and distinguishes the egress and invasion steps, the researchers said.
"When the parasite gets out of the red blood cell, it has a matter of seconds or minutes to get into new red blood cells, or it will be cleared or killed by the human immune system," said first author Jeffrey Dvorin, a postdoctoral research fellow in the Duraisingh Lab at HSPH and a clinical fellow in pediatric infectious diseases at Children's Hospital Boston. "We found an important trigger for the parasite to exit cells that may be independent from the invasion trigger."
Even better, the protein is found in the parasite and in plants, but not in humans, which means a drug targeted to that protein may be less toxic for people. The protein belongs to a family of Plasmodium falciparum calcium-dependent protein kinases, or PfCDPK5 for short in this case. Other members of the family have been implicated in parasite egress of red blood cells, but this is the first study using a genetic technique to validate a protein critical for parasite egress of red blood cells, according to the researchers.
Many companies and labs are looking for inhibitors of parasite egress and invasion of red blood cells, but no anti-malarial drugs yet target these stages of the parasite lifecycle, Dvorin said.
The paper also demonstrates the usefulness of a new tool that can be used to evaluate additional members of the kinase family, as well as other signaling pathways that regulate key events in the blood stage of malaria infection. As of 2002, "we have a malaria genome of about 6,000 genes," said Duraisingh. "We need a means of prioritizing specific gene candidates for further drug development."
http://www.sciencecodex.com/new_twist_on_potential_malaria_drug_target_acts_by_trapping_parasites_in_cells
MALARIA: Cleaner environment lowers incidence
For over half a century, the battle against malaria has been waged with powerful anti-malarial drugs and potent mosquito-killing insecticides, weapons born from the wonders of synthetic chemistry. In recent years, however, fed up with the financial and ecological drawbacks of chemical warfare, malarious communities from China to Tanzania to Mexico have been forging a new way to fight the scourge, one that draws inspiration from the lessons of ecology more than chemistry. Rather than attempt to destroy mosquitoes and parasites outright, these new methods call for subtle manipulations of human habitats and the draining of local water bodies — from puddles to irrigation canals — where malarial mosquitoes hatch.The most striking example comes from Mexico, which has completely abandoned its previously lavish use of DDT in malaria control for insecticide-free methods and has seen malaria cases plummet.Like many countries, Mexico for decades relied upon insecticides to fight the disease, by spraying mosquito-killing chemicals on the interior walls of homes where blood-feeding mosquitoes rest, among other methods. Between 1957 and 1999, taming Mexico’s malaria required 70,000 tons of DDT.New, environmentally-sensitive methods, such as clearing vegetation along waterways and around homes, were introduced in Oaxaca, the country’s most malarious region, in 1998. By 2002, malaria cases had fallen from more than 17,500 to just 254, and Mexico incorporated the new methods
In Oaxaca, officials recruited volunteers to remove algae and trash from rivers and streams.into its national anti-malaria program. By 2000, Mexico had completely phased out use of DDT in malaria control; by 2002, it had phased out all other insecticides in malaria control as well, while simultaneously keeping malaria in check. No deaths from malaria were reported in Mexico in 2008, the most recent year of data available from the World Health Organization.Similarly, in Sichuan, China, new, non-chemical methods involving the manipulation of water flow in irrigation canals have led to the near cessation of malaria, with malaria rates plummeting from 4 per 10,000 in 1993, to less than 1 per 10,000 by 2004. In several counties of the province, no malaria cases were reported at all between 2001 and 2004. Similar non-chemical gains against the disease have been achieved in Dar es Salaam, Tanzania, as well.
http://www.e360.yale.edu/content/feature.msp?id=2270
In Oaxaca, officials recruited volunteers to remove algae and trash from rivers and streams.into its national anti-malaria program. By 2000, Mexico had completely phased out use of DDT in malaria control; by 2002, it had phased out all other insecticides in malaria control as well, while simultaneously keeping malaria in check. No deaths from malaria were reported in Mexico in 2008, the most recent year of data available from the World Health Organization.Similarly, in Sichuan, China, new, non-chemical methods involving the manipulation of water flow in irrigation canals have led to the near cessation of malaria, with malaria rates plummeting from 4 per 10,000 in 1993, to less than 1 per 10,000 by 2004. In several counties of the province, no malaria cases were reported at all between 2001 and 2004. Similar non-chemical gains against the disease have been achieved in Dar es Salaam, Tanzania, as well.
http://www.e360.yale.edu/content/feature.msp?id=2270
MALARIA: Rwanda success
Just over five years ago, malaria was Rwanda's number one killer. But working closely with international donors and partners, Rwanda's National Malaria Control Program put together a multifaceted approach that, in a mere 18 months, cut the number of malaria deaths across the country by more than half. The project's two main tools - long-lasting insecticide-treated nets and WHO-recommended anti-malarial drugs - did not differ significantly from approaches used in other malaria-endemic countries. What did differ was the strong leadership of the Rwandan government that paved the way for success. For me, it is the overall thrust of that too rare effort - rather than the details - that can provide lessons for development aid beyond public health. Three years ago, Rwanda intensely scaled up its malaria interventions by aligning international partners to its aggressive, comprehensive and country-specific national strategy. In effect, they threw the most effective malaria interventions available at the disease and reshaped the government's health care and financing focus to achieve superior results.
With new resources from the Global Fund to Fight AIDS, Tuberculosis and Malaria, Rwanda initiated an aggressive campaign and managed to deliver an unprecedented number of mosquito nets to vulnerable communities across the country. But they knew that prevention was only part of their very specific battle against malaria, so Rwandan leaders worked to strengthen their health care system through innovative financing strategies and increased access to the most effective malaria treatment drugs where they were needed most: in the community. Ultimately, what allowed for the success of these strategies was the collaboration of partners fostered by the local leadership - a host of international and national NGOs including PSI, United Nations agencies, and funders such as the U.S. President's Malaria Initiative and the Global Fund. While the partners provided resources and expertise, Rwandan leadership ensured efficient use of funds.
http://www.huffingtonpost.com/karl-hofmann/lessons-from-africa-the-l_b_573226.html
With new resources from the Global Fund to Fight AIDS, Tuberculosis and Malaria, Rwanda initiated an aggressive campaign and managed to deliver an unprecedented number of mosquito nets to vulnerable communities across the country. But they knew that prevention was only part of their very specific battle against malaria, so Rwandan leaders worked to strengthen their health care system through innovative financing strategies and increased access to the most effective malaria treatment drugs where they were needed most: in the community. Ultimately, what allowed for the success of these strategies was the collaboration of partners fostered by the local leadership - a host of international and national NGOs including PSI, United Nations agencies, and funders such as the U.S. President's Malaria Initiative and the Global Fund. While the partners provided resources and expertise, Rwandan leadership ensured efficient use of funds.
http://www.huffingtonpost.com/karl-hofmann/lessons-from-africa-the-l_b_573226.html
MALARIA: Adaptive mechanisms of P Falciparum
Malaria parasites have to survive and transmit within a highly selective and ever-changing host environment. Because immunity to malaria is nonsterilizing and builds up slowly through repeated infections, commonly the parasite invades a host that is immunologically and physiologically different from its previous host. During the course of infection, the parasite must also keep pace with changes in host immune responses and red-blood-cell physiology. Here, we describe the "selection landscape" of the most virulent of the human malaria parasites, Plasmodium falciparum, and the adaptive mechanisms it uses to navigate through that landscape. Taking a cost-benefit view of parasite fitness, we consider the evolutionary outcomes of the most important forces of selection operating on the parasite, namely immunity, host death, drugs, mosquito availability, and coinfection. Given the huge potential for malaria parasite evolution in the context of the recently renewed effort to eradicate malaria, a deeper understanding of P. falciparum adaptation is essential.
http://www.sciencemag.org/cgi/content/abstract/328/5980/866
http://www.sciencemag.org/cgi/content/abstract/328/5980/866
Seattle BioMed has been hot on the heels of Big Pharma giant GlaxoSmithKline, which is in the last of three phases of clinical trials with a vaccine candidate. The Glaxo vaccine, RTS,S has shown an ability to protect about half of people from the parasite, which causes nasty anemia that can be fatal, especially for children in sub-Saharan Africa. Seattle BioMed isn’t satisfied with that amount of protection, and is shooting for a vaccine that offer 90 percent protection.
Seattle BioMed has developed a live, weakened form of the malaria parasite as the key ingredient in its vaccine candidate. This trial, posted already on clinicaltrials.gov, is designed to enroll 32 healthy volunteers at a single site, Walter Reed Army Institute of Research in Silver Spring, MD. They will be given five doses of vaccine, four weeks apart. And here’s the kicker—the vaccine will be “challenged” when the volunteers are exposed and bitten by mosquitos carrying real malaria. These people, obviously, are going to be monitored extremely carefully, and if the vaccine doesn’t appear to be protecting them right away, they will be given a drug to treat the malaria before it starts causing problems for the volunteers.
http://www.xconomy.com/seattle/2010/03/26/nine-years-in-the-making-seattle-biomeds-malaria-vaccine-on-verge-of-first-human-trial/
Seattle BioMed has developed a live, weakened form of the malaria parasite as the key ingredient in its vaccine candidate. This trial, posted already on clinicaltrials.gov, is designed to enroll 32 healthy volunteers at a single site, Walter Reed Army Institute of Research in Silver Spring, MD. They will be given five doses of vaccine, four weeks apart. And here’s the kicker—the vaccine will be “challenged” when the volunteers are exposed and bitten by mosquitos carrying real malaria. These people, obviously, are going to be monitored extremely carefully, and if the vaccine doesn’t appear to be protecting them right away, they will be given a drug to treat the malaria before it starts causing problems for the volunteers.
http://www.xconomy.com/seattle/2010/03/26/nine-years-in-the-making-seattle-biomeds-malaria-vaccine-on-verge-of-first-human-trial/
Monday, 24 May 2010
MALARIA: Haiti
Recent calls to eliminate malaria from Hispaniola — the last Caribbean island with endemic transmission of Plasmodium falciparum — are timely and important, write Joseph Keating, Donald Krogstad and Thomas Eisel from Tulane University in the United States in The Lancet Infectious Diseases.
It would provide proof of principle that malaria elimination is possible in complex environments. But elimination is also needed because there is now evidence of chloroquine resistance in Haiti and fast action is needed before the country is forced to switch to a more expensive combination therapy.
Lessons learnt in Haiti will be critical for informing other countries seeking malaria elimination. If elimination cannot be achieved on this small Caribbean island, there is little hope that it can be achieved in Sub-Saharan Africa where the malaria burden is higher and its control more complicated, say the authors.
But they add that elimination strategies used on the island should not be oversimplistic adaptation of control measures used in Africa or other endemic areas.
The key to eliminating malaria in Hispaniola lies in using a combination of methods to eliminate the parasite reservoir in human beings, prevent transmission and mobilise the community to seek out diagnosis and treatment.
All this requires unshakeable political will.
The cost of eliminating malaria in Hispaniola may be high — but it would set a precedent for health diplomacy and is a prerequisite to any global malaria elimination campaign.
http://www.scidev.net/en/opinions/why-we-must-eliminate-malaria-from-hispaniola.html
It would provide proof of principle that malaria elimination is possible in complex environments. But elimination is also needed because there is now evidence of chloroquine resistance in Haiti and fast action is needed before the country is forced to switch to a more expensive combination therapy.
Lessons learnt in Haiti will be critical for informing other countries seeking malaria elimination. If elimination cannot be achieved on this small Caribbean island, there is little hope that it can be achieved in Sub-Saharan Africa where the malaria burden is higher and its control more complicated, say the authors.
But they add that elimination strategies used on the island should not be oversimplistic adaptation of control measures used in Africa or other endemic areas.
The key to eliminating malaria in Hispaniola lies in using a combination of methods to eliminate the parasite reservoir in human beings, prevent transmission and mobilise the community to seek out diagnosis and treatment.
All this requires unshakeable political will.
The cost of eliminating malaria in Hispaniola may be high — but it would set a precedent for health diplomacy and is a prerequisite to any global malaria elimination campaign.
http://www.scidev.net/en/opinions/why-we-must-eliminate-malaria-from-hispaniola.html
MALARIA: Stategy to Combat Malaria
Across the continent, malaria control programs are scaling up efforts to protect people from this deadly disease and to diagnosis and treat infections with highly effective new drugs. Emerging data are showing significant reductions in malarial illnesses and deaths.
Partnerships with national governments and development partners, including, the Global Fund to Fight AIDS, Tuberculosis and Malaria, the World Bank Booster Program for Malaria Control, the Bill and Melinda Gates Foundation, and the UN Envoy for Malaria, which has mobilized thousands of partners with the goal of reaching the universal coverage of long lasting insecticide treated bed-nets by the end of this year, have made these successes possible.
The results in global malaria prevention and control are encouraging, but, as before, this progress is fragile and can be easily reversed. Therefore, as we expand and consolidate these gains, it is vitally important to ensure that our efforts not only sustain momentum, but also continue to adapt to emerging challenges.
Today, I am proud to release the U.S. Government six-year strategy to combat malaria (pdf) globally. By 2014, our goal is to halve malaria illnesses and deaths in 70 percent of at-risk populations, by accelerating and intensifying malaria control efforts in the high burden countries of sub-Saharan Africa. The release of the President’s Malaria Initiative whole-of-government global strategy also outlines contributions to stop the spread of multi-drug resistance in Southeast Asia and the Americas; increase emphasis on strategic integration of malaria prevention and treatment activities with programs for maternal and child health, HIV/AIDS, neglected tropical diseases, and tuberculosis, through multilateral collaboration to achieve internationally-accepted goals; and intensify efforts to strengthen health systems.
The U.S. Government’s commitment to fight malaria is a key component of President Obama’s foreign assistance strategy and his Administration’s Global Health Initiative -- a global commitment to invest in healthy and productive lives and maximize the sustainable health impact the United States achieves for every dollar invested.
http://www.whitehouse.gov/blog/2010/04/23/us-expands-anti-malaria-effort-progress-takes-hold
Partnerships with national governments and development partners, including, the Global Fund to Fight AIDS, Tuberculosis and Malaria, the World Bank Booster Program for Malaria Control, the Bill and Melinda Gates Foundation, and the UN Envoy for Malaria, which has mobilized thousands of partners with the goal of reaching the universal coverage of long lasting insecticide treated bed-nets by the end of this year, have made these successes possible.
The results in global malaria prevention and control are encouraging, but, as before, this progress is fragile and can be easily reversed. Therefore, as we expand and consolidate these gains, it is vitally important to ensure that our efforts not only sustain momentum, but also continue to adapt to emerging challenges.
Today, I am proud to release the U.S. Government six-year strategy to combat malaria (pdf) globally. By 2014, our goal is to halve malaria illnesses and deaths in 70 percent of at-risk populations, by accelerating and intensifying malaria control efforts in the high burden countries of sub-Saharan Africa. The release of the President’s Malaria Initiative whole-of-government global strategy also outlines contributions to stop the spread of multi-drug resistance in Southeast Asia and the Americas; increase emphasis on strategic integration of malaria prevention and treatment activities with programs for maternal and child health, HIV/AIDS, neglected tropical diseases, and tuberculosis, through multilateral collaboration to achieve internationally-accepted goals; and intensify efforts to strengthen health systems.
The U.S. Government’s commitment to fight malaria is a key component of President Obama’s foreign assistance strategy and his Administration’s Global Health Initiative -- a global commitment to invest in healthy and productive lives and maximize the sustainable health impact the United States achieves for every dollar invested.
http://www.whitehouse.gov/blog/2010/04/23/us-expands-anti-malaria-effort-progress-takes-hold
MALARIA: anAPN1 antigen
Malaria was eradicated in the U.S. by 1951, so Americans can be forgiven for not giving the disease much thought. But the mosquito-borne scourge is responsible for the deaths of nearly a million children under age 5 each year — mostly in Africa — killing one child every 30 seconds. Half the world's population remains at risk — including travelers to affected countries.
But while initiatives to provide insecticide-treated bed nets and other control measures have cut malaria rates in half in some countries, the disease is adapting, and insecticide-resistant and treatment-resistant strains are increasingly problematic. And the worldwide recession is reducing the funding available to keep malaria-control initiatives going. As a new avenue of attack, the PATH Malaria Vaccine Initiative (MVI) — which is funded by the Bill & Melinda Gates Foundation — on Friday, Jan. 15, announced a collaboration with the Johns Hopkins Bloomberg School of Public Health and the Sabin Vaccine Institute to create a whole new kind of malaria vaccine. Called a transmission-blocking vaccine (TBV), it is aimed not at protecting individuals from the disease but at preventing mosquitoes that carry it from spreading it.
"I think it's very encouraging," says Dr. Lee Hall, chief of the Parasitology and International Programs branch of the National Institute of Allergy and Infectious Diseases (NIAID). "It's a big endorsement by MVI for this general approach."
Traditional vaccines work by introducing a killed or weakened version of a disease into the body, where the immune system spots it and cranks out antibodies against it. Then, if a wild strain of the pathogen comes along later — one that has the power to sicken or kill — the body is ready for it. The new approach is different. Developed by Rhoel Dinglasan, an entomologist and biologist at Johns Hopkins University Hospital, it would instead work within the mosquito gut.
Dinglasan has found an antigen, called AnAPN1, that causes humans to create antibodies that prevent transmission of malaria by mosquitoes. Get enough of these antibodies into mosquitoes, and you lock the disease up there and prevent it from infecting us. Sounds good, but how do you implement such a strategy? You can hardly vaccinate the mosquitoes themselves. Instead, you put the AnAPN1 into their food source: us. A mosquito that bites an inoculated person would pick up the antibodies and then be sidelined from the malaria-transmission game.
The new vaccine is not the first TBV attempted. Previous versions used not AnAPN1 but parts of the malaria parasite to generate human immune responses. Unfortunately, two vaccine candidates using that approach unexpectedly caused some skin disorders when tested in humans in 2008, prompting a need for further research. And even without that side effect, using antigens from the malaria parasite would require multiple vaccines to fight the many different strains of malaria.
Malaria TBVs can be problematic, and not just because none has been perfected yet. People would have to step forward to receive a vaccine that would not make them immune to malaria; they would instead become part of a growing web of people who would eventually push the parasite out of circulation. That complicates the risk-benefit calculus. Every vaccine, after all, can have side effects — in some cases, the possibility of contracting the disease itself. Typically, people are willing to accept that danger because they want the immunity. The AnAPN1 vaccine has been tested in human blood only in the lab, and while it's effective there, no one knows if it causes any negative reactions in people.
To make a TBV more more attractive, then, epidemiologists do not plan to administer it by itself. Rather, it would be given along with a traditional immunity-conferring vaccine. "Not a single person thinks that you should give a transmission-blocking vaccine alone," says Dinglasan. "You'd give it in combination."
This would also help the vaccine get past regulators at agencies like the FDA. Medications are approved based on an "indication," a medical problem or risk suffered by an individual. If a TBV were not part of a combination vaccine, this "indication" would be hard to define. Of course, the traditional vaccine that would make the TBV acceptable doesn't exist yet either, but progress is being made on that front. Right now, for example, PATH MVI is testing a vaccine called RTSS, which reduced risk of infection for one strain of the disease at least 50% in late-stage clinical trials for 16,000 infants in Africa — not perfect, but still useful in places where 25% of infant deaths are caused by malaria.
It's Dinglasan's TBV, though, that's really sparking the excitement in the field. One reason is its robustness. The vaccine so far works against the major types of malaria and all species of mosquitoes tested — critical if the disease is going to be not just controlled but snuffed out entirely. "We're working towards eventual eradication," explains Dr. Ashley Birkett, director of preclinical research and development at PATH MVI. "It requires a long-term vision, and we really think a vaccine that can block transmission from one person to another is going to be a critical tool."
Not only would malaria eradication save millions of lives, it would also free up many countries from the crushing costs of dealing with the disease — costs that make economic growth impossible. The American economy, when it is not in recession, has typically grown about 3% per year since the 1970s. Countries with malaria, by contrast, lose 1.3% of that potential growth — nearly half — just to the consequences of the disease, according to a study by leading global economist Jeffrey Sachs. "It's like a huge tax on economic growth," says Hall.
Dinglasan — who comes from the Philippines, where some islands are still affected by malaria — sees things in a more basic way. Malaria, he says, is "a dark cloud. We're talking about the deaths of small children. They can't get past the age of 5. I don't know if you can measure the full impact of that." You can't. Nor can you measure the sense of global relief when that kind of suffering is over for good.
http://www.time.com/time/health/article/0,8599,1954177,00.html#ixzz0oqWJctjB
But while initiatives to provide insecticide-treated bed nets and other control measures have cut malaria rates in half in some countries, the disease is adapting, and insecticide-resistant and treatment-resistant strains are increasingly problematic. And the worldwide recession is reducing the funding available to keep malaria-control initiatives going. As a new avenue of attack, the PATH Malaria Vaccine Initiative (MVI) — which is funded by the Bill & Melinda Gates Foundation — on Friday, Jan. 15, announced a collaboration with the Johns Hopkins Bloomberg School of Public Health and the Sabin Vaccine Institute to create a whole new kind of malaria vaccine. Called a transmission-blocking vaccine (TBV), it is aimed not at protecting individuals from the disease but at preventing mosquitoes that carry it from spreading it.
"I think it's very encouraging," says Dr. Lee Hall, chief of the Parasitology and International Programs branch of the National Institute of Allergy and Infectious Diseases (NIAID). "It's a big endorsement by MVI for this general approach."
Traditional vaccines work by introducing a killed or weakened version of a disease into the body, where the immune system spots it and cranks out antibodies against it. Then, if a wild strain of the pathogen comes along later — one that has the power to sicken or kill — the body is ready for it. The new approach is different. Developed by Rhoel Dinglasan, an entomologist and biologist at Johns Hopkins University Hospital, it would instead work within the mosquito gut.
Dinglasan has found an antigen, called AnAPN1, that causes humans to create antibodies that prevent transmission of malaria by mosquitoes. Get enough of these antibodies into mosquitoes, and you lock the disease up there and prevent it from infecting us. Sounds good, but how do you implement such a strategy? You can hardly vaccinate the mosquitoes themselves. Instead, you put the AnAPN1 into their food source: us. A mosquito that bites an inoculated person would pick up the antibodies and then be sidelined from the malaria-transmission game.
The new vaccine is not the first TBV attempted. Previous versions used not AnAPN1 but parts of the malaria parasite to generate human immune responses. Unfortunately, two vaccine candidates using that approach unexpectedly caused some skin disorders when tested in humans in 2008, prompting a need for further research. And even without that side effect, using antigens from the malaria parasite would require multiple vaccines to fight the many different strains of malaria.
Malaria TBVs can be problematic, and not just because none has been perfected yet. People would have to step forward to receive a vaccine that would not make them immune to malaria; they would instead become part of a growing web of people who would eventually push the parasite out of circulation. That complicates the risk-benefit calculus. Every vaccine, after all, can have side effects — in some cases, the possibility of contracting the disease itself. Typically, people are willing to accept that danger because they want the immunity. The AnAPN1 vaccine has been tested in human blood only in the lab, and while it's effective there, no one knows if it causes any negative reactions in people.
To make a TBV more more attractive, then, epidemiologists do not plan to administer it by itself. Rather, it would be given along with a traditional immunity-conferring vaccine. "Not a single person thinks that you should give a transmission-blocking vaccine alone," says Dinglasan. "You'd give it in combination."
This would also help the vaccine get past regulators at agencies like the FDA. Medications are approved based on an "indication," a medical problem or risk suffered by an individual. If a TBV were not part of a combination vaccine, this "indication" would be hard to define. Of course, the traditional vaccine that would make the TBV acceptable doesn't exist yet either, but progress is being made on that front. Right now, for example, PATH MVI is testing a vaccine called RTSS, which reduced risk of infection for one strain of the disease at least 50% in late-stage clinical trials for 16,000 infants in Africa — not perfect, but still useful in places where 25% of infant deaths are caused by malaria.
It's Dinglasan's TBV, though, that's really sparking the excitement in the field. One reason is its robustness. The vaccine so far works against the major types of malaria and all species of mosquitoes tested — critical if the disease is going to be not just controlled but snuffed out entirely. "We're working towards eventual eradication," explains Dr. Ashley Birkett, director of preclinical research and development at PATH MVI. "It requires a long-term vision, and we really think a vaccine that can block transmission from one person to another is going to be a critical tool."
Not only would malaria eradication save millions of lives, it would also free up many countries from the crushing costs of dealing with the disease — costs that make economic growth impossible. The American economy, when it is not in recession, has typically grown about 3% per year since the 1970s. Countries with malaria, by contrast, lose 1.3% of that potential growth — nearly half — just to the consequences of the disease, according to a study by leading global economist Jeffrey Sachs. "It's like a huge tax on economic growth," says Hall.
Dinglasan — who comes from the Philippines, where some islands are still affected by malaria — sees things in a more basic way. Malaria, he says, is "a dark cloud. We're talking about the deaths of small children. They can't get past the age of 5. I don't know if you can measure the full impact of that." You can't. Nor can you measure the sense of global relief when that kind of suffering is over for good.
http://www.time.com/time/health/article/0,8599,1954177,00.html#ixzz0oqWJctjB
MALARIA: AnAPN1 Antigen
But mosquitoes, those clever little pests, are getting wise. In some parts of the world, mosquitoes have become immune to certain strains of anti-malarial drugs. In other parts of the world, they're adapting around insecticides in which thousands of bednets have been dipped.
So latest malaria drug doesn't try to protect the human body from malaria. Instead, it uses the human body to target the mosquito.
Rhoel Dinglasan, a John Hopkins University biologist, discovered that something called the 'AnAPN1 antigen' can block mosquitoes from transmitting malaria. But the mosquito has to ingest the antigen, first. Enter the human body as vessel of vaccine: While we take the pill containing the antigen, we're not the target. We're the conduit, the link between the AnAPN1 and the hungry mosquito — which gets a little dose of that antigen when it feeds on our skin. After a big enough meal, it's hoped, the mosquito won't be able to transmit malaria any longer.
But the drug is still being researched, and as Bill Gates can tell you, malaria research isn't cheap, nor is it a cause celebre. Malaria was eradicated in the U.S. in the 1950s, making it difficult to drum up support for the massive research dollars a treatment-and-prevent effort takes
http://globalpoverty.change.org/blog/view/drugging_mosquitoes_to_fight_malaria
So latest malaria drug doesn't try to protect the human body from malaria. Instead, it uses the human body to target the mosquito.
Rhoel Dinglasan, a John Hopkins University biologist, discovered that something called the 'AnAPN1 antigen' can block mosquitoes from transmitting malaria. But the mosquito has to ingest the antigen, first. Enter the human body as vessel of vaccine: While we take the pill containing the antigen, we're not the target. We're the conduit, the link between the AnAPN1 and the hungry mosquito — which gets a little dose of that antigen when it feeds on our skin. After a big enough meal, it's hoped, the mosquito won't be able to transmit malaria any longer.
But the drug is still being researched, and as Bill Gates can tell you, malaria research isn't cheap, nor is it a cause celebre. Malaria was eradicated in the U.S. in the 1950s, making it difficult to drum up support for the massive research dollars a treatment-and-prevent effort takes
http://globalpoverty.change.org/blog/view/drugging_mosquitoes_to_fight_malaria
MALARIA: Roads affect ability to prevent
Decaying road infrastructure in Binga district, in Zimbabwe's province of Matabeleland North, prevented anti-malaria spraying teams from reaching the area, and is being blamed for an outbreak of the mosquito-borne disease. Health officials told IRIN that hospitals and clinics in the remote and humid district in the Zambezi valley on the border with Zambia, have recorded 90 percent of the province's malaria cases this year: 4,500 cases in the past four months, resulting in 14 fatalities. Zimbabwe's economic malaise has put off upgrading or maintenance of much of its existing road infrastructure, while flooding rivers have limited the ability of health ministry teams to carry out preventative spraying of dwellings and mosquito breeding grounds, such as stagnant water, particularly in rural areas. "At one time I spent four hours waiting for the river to subside from a low bridge before we were able to get to the other side," said acting provincial medical director Dr Paul Hazangue after a recent visit to the area. "We received more malaria cases from Binga largely due to intermittent rains experienced in that district - mosquitoes breed and mature faster in such weather conditions." Hazangue said the Ministry of Health and Child Welfare had set up malaria management courses for nurses at rural clinics, and had established satellite clinics in the districts of Lupane, Hwange, Tsholotsho and Nkayi.
http://globalpolicy.org/component/content/article/211-development/49064-zimbabwe-bad-roads-lead-to-malaria-outbreak-.html
http://globalpolicy.org/component/content/article/211-development/49064-zimbabwe-bad-roads-lead-to-malaria-outbreak-.html
MALARIA: Haiti
On top of the almost unimaginable devastation caused by January's earthquake in Haiti, the nation is bracing for the ravages of the rainy season. Torrential downpours have already flooded homes and turned tent cities into muddy misery. Ominously, the number of cases of malaria, which is spread by the bite of mosquitoes and which was endemic in Haiti even before the earthquake, is increasing.
To reduce the incidence of malaria, various aid groups are planning to distribute more than 3 million bed nets, an ultra-low-tech, only modestly effective intervention. What is really needed is the chemical DDT, an old, cheap and safe tool to control the vector -- the Anopheles mosquito -- that spreads the disease.
Malaria is a scourge of humanity, particularly for the inhabitants of poor tropical countries. Forty-one percent of the world's population live in areas where malaria is transmitted, and each year 350 to 500 million cases of malaria occur worldwide. The disease imposes huge costs on individuals, families and governments, which are a crushing economic burden on malaria-endemic countries and impede their economic growth. It has been estimated that economic growth per year of countries with a high incidence of malaria was 1.3 percentage points lower than that of similar countries without malaria.
A drug called chloroquine is a useful preventive but many strains of the malaria parasite in Haiti have developed resistance to it. Other drugs called artemisinins are safe and exhibit potent, rapid antimalarial activity, and in combination with other anti-malarials they have been used effectively for several years to treat multiple-drug-resistant malaria. But resistance has arisen and is increasing, so that in the absence of a vaccine elimination of the mosquitoes that spread the disease is the key to preventing epidemics.
Unfortunately, flawed public policy limits the available options.
In 1972, on the basis of data on toxicity to fish and migrating birds (but not to humans), the U.S. Environmental Protection Agency banned virtually all uses of the pesticide DDT, an inexpensive and effective pesticide once widely deployed to kill disease-carrying insects. DDT was subsequently banned for agricultural use worldwide under the 2001 Stockholm Convention on Persistent Organic Pollutants, which stigmatized the chemical and effectively constituted a prohibition.
Although DDT is a (modestly) toxic substance, there is a vast difference between applying large amounts of it in the environment -- as farmers did before it was banned -- and using it carefully and sparingly to fight mosquitoes and other disease-carrying insects. DDT remains largely near where it is sprayed, and no study has ever linked environmental exposure to DDT to harm to human health.
When DDT is used at all now, it is sprayed indoors in small amounts to prevent mosquitoes from nesting, so exposures would be low. A basic principle of toxicology is that the dose makes the poison, and with modern regimens, both environmental and human exposures would be very low.
The regulators who banned DDT failed to take into consideration the inadequacy of alternatives. Because it persists after spraying, DDT works far better than many pesticides now in use, some of which are toxic to fish and other aquatic organisms. With DDT unavailable, many mosquito-control authorities are depleting their budgets by repeated spraying with short-acting, marginally effective insecticides. Read more: http://www.miamiherald.com/2010/05/03/1610610/ddt-can-stymie-malaria-carrying.html#ixzz0oqSp6Fr8
To reduce the incidence of malaria, various aid groups are planning to distribute more than 3 million bed nets, an ultra-low-tech, only modestly effective intervention. What is really needed is the chemical DDT, an old, cheap and safe tool to control the vector -- the Anopheles mosquito -- that spreads the disease.
Malaria is a scourge of humanity, particularly for the inhabitants of poor tropical countries. Forty-one percent of the world's population live in areas where malaria is transmitted, and each year 350 to 500 million cases of malaria occur worldwide. The disease imposes huge costs on individuals, families and governments, which are a crushing economic burden on malaria-endemic countries and impede their economic growth. It has been estimated that economic growth per year of countries with a high incidence of malaria was 1.3 percentage points lower than that of similar countries without malaria.
A drug called chloroquine is a useful preventive but many strains of the malaria parasite in Haiti have developed resistance to it. Other drugs called artemisinins are safe and exhibit potent, rapid antimalarial activity, and in combination with other anti-malarials they have been used effectively for several years to treat multiple-drug-resistant malaria. But resistance has arisen and is increasing, so that in the absence of a vaccine elimination of the mosquitoes that spread the disease is the key to preventing epidemics.
Unfortunately, flawed public policy limits the available options.
In 1972, on the basis of data on toxicity to fish and migrating birds (but not to humans), the U.S. Environmental Protection Agency banned virtually all uses of the pesticide DDT, an inexpensive and effective pesticide once widely deployed to kill disease-carrying insects. DDT was subsequently banned for agricultural use worldwide under the 2001 Stockholm Convention on Persistent Organic Pollutants, which stigmatized the chemical and effectively constituted a prohibition.
Although DDT is a (modestly) toxic substance, there is a vast difference between applying large amounts of it in the environment -- as farmers did before it was banned -- and using it carefully and sparingly to fight mosquitoes and other disease-carrying insects. DDT remains largely near where it is sprayed, and no study has ever linked environmental exposure to DDT to harm to human health.
When DDT is used at all now, it is sprayed indoors in small amounts to prevent mosquitoes from nesting, so exposures would be low. A basic principle of toxicology is that the dose makes the poison, and with modern regimens, both environmental and human exposures would be very low.
The regulators who banned DDT failed to take into consideration the inadequacy of alternatives. Because it persists after spraying, DDT works far better than many pesticides now in use, some of which are toxic to fish and other aquatic organisms. With DDT unavailable, many mosquito-control authorities are depleting their budgets by repeated spraying with short-acting, marginally effective insecticides. Read more: http://www.miamiherald.com/2010/05/03/1610610/ddt-can-stymie-malaria-carrying.html#ixzz0oqSp6Fr8
MALARIA: Three prong approach
About one million people die every year worldwide from the disease, of whom 85 percent are in Africa, Kikwete said.
"We believe that if we cover everybody in Africa with bed nets, insecticides and medication by the end of this year, we will have zero deaths or near zero deaths from malaria in Africa by 2015," said Ray Chambers, a U.N. special envoy for malaria.
This three-pronged approach had cut malaria cases in the archipelago of Zanzibar to below 1 percent from 40 percent, Kikwete told a news conference of the African Leaders Malaria Alliance on the sidelines of the World Economic Forum on Africa.
U.S. Malaria Coordinator Timothy Ziemer said the U.S. government has made a budget request of $680 million for the fight against malaria in 2011. That includes $100 million for the Democratic Republic of Congo and Nigeria, which together account for about half of the world's malaria cases.
Malaria is caused by parasites transmitted to humans through the bite of an infected mosquito. The disease costs Africa over $40 billion a year in treatment and sick days.
http://www.reuters.com/article/idUSTRE6445H220100505
"We believe that if we cover everybody in Africa with bed nets, insecticides and medication by the end of this year, we will have zero deaths or near zero deaths from malaria in Africa by 2015," said Ray Chambers, a U.N. special envoy for malaria.
This three-pronged approach had cut malaria cases in the archipelago of Zanzibar to below 1 percent from 40 percent, Kikwete told a news conference of the African Leaders Malaria Alliance on the sidelines of the World Economic Forum on Africa.
U.S. Malaria Coordinator Timothy Ziemer said the U.S. government has made a budget request of $680 million for the fight against malaria in 2011. That includes $100 million for the Democratic Republic of Congo and Nigeria, which together account for about half of the world's malaria cases.
Malaria is caused by parasites transmitted to humans through the bite of an infected mosquito. The disease costs Africa over $40 billion a year in treatment and sick days.
http://www.reuters.com/article/idUSTRE6445H220100505
Thursday, 20 May 2010
MALARIA: Indonesia targets pregnant women and children
JAKARTA, 20 May 2010 (IRIN) - Health authorities are successfully battling malaria in remote eastern Indonesia by linking efforts to fight the mosquito-borne disease to maternal and child healthcare."Pregnant women and children are especially vulnerable to malaria, and modern malaria diagnosis and prevention can be delivered via existing maternal health and immunisation services in a symbiotic way," said William Hawley, a malaria expert formerly with the UN Children's Fund (UNICEF) [http://www.unicef.org/].Nurses and midwives help the malaria programme with diagnosis, treatment and bed net distribution, Hawley said. Furthermore, because people want bed nets, more women use antenatal care and bring their children to be immunised."The malaria programme, the antenatal care programme, and the expanded programme on immunisation all benefit, but most important - women and kids benefit," Hawley said.Malaria was once the top health problem in South Halmahera District - 400 islets inhabited by 200,000 people in North Maluku Province, health officials say.Swamps, poor sanitation, poverty and low levels of immunisation left the population - pregnant women and children in particular - vulnerable to health problems.By integrating prevention, diagnosis and treatment with antenatal care and child immunisation, the number of malaria deaths in South Halmahera plummeted from 226 in 2003 to four in 2008, and the incidence of malaria dropped by 50 percent, according to the district health office.
Wednesday, 19 May 2010
MALARIA: locking in the parasite!
Harvard School of Public Health (HSPH) researchers and colleagues seeking to block invasion of healthy red blood cells by malaria parasites have instead succeeded in locking the parasites within infected blood cells, potentially containing the disease.
The findings reveal an essential step in the biology of the most common and severe malaria parasite, Plasmodium falciparum, and offer a new drug target for fighting one of the world's most common and dangerous infections.
Malaria sickens up to one half billion people every year and kills up to one million, mostly children in sub-Saharan Africa. The high fevers, shaking chills, flu-like symptoms, and anemia can be fatal unless treated quickly. Malaria has grown resistant to a long list of drugs, and vaccines are still in experimental stages.
Working with the malaria parasite and human blood in test tubes and lab dishes, the research team identified a single fast-acting protein in the parasite that enables it and several dozen of its offspring to escape from a human red blood cell in preparation for quick invasion of many more healthy blood cells. Eliminating that protein traps the parasites in the cell.
After an infected mosquito bites a person, malaria parasites move into the liver, where they silently mature and multiply within weeks. Malaria parasites make people sick weeks or months later when they enter red blood cells and begin an exponential expansion. In a single cell, a parasite produces up to 32 offspring in about two days, which burst out to infect more red blood cells.
"This is the stage where things have to happen very fast for the parasite," said senior author Manoj Duraisingh, HSPH assistant professor of immunology and infectious diseases and senior author of the paper in the May 14 Science. "The parasite doesn't like to spend much time outside the cell. It grows and matures, and immediately following rupture, enters a new cell. It was a surprise that this protein kinase, which we thought would be involved in red blood cell invasion, turns out to be essential for the parasite getting out of the cell."
The study helps define the exit of the parasite from a blood cell as a highly choreographed process and distinguishes the egress and invasion steps, the researchers said.
"When the parasite gets out of the red blood cell, it has a matter of seconds or minutes to get into new red blood cells, or it will be cleared or killed by the human immune system," said first author Jeffrey Dvorin, a postdoctoral research fellow in the Duraisingh Lab at HSPH and a clinical fellow in pediatric infectious diseases at Children's Hospital Boston. "We found an important trigger for the parasite to exit cells that may be independent from the invasion trigger
http://www.sciencedaily.com/releases/2010/05/100514171912.htm
The findings reveal an essential step in the biology of the most common and severe malaria parasite, Plasmodium falciparum, and offer a new drug target for fighting one of the world's most common and dangerous infections.
Malaria sickens up to one half billion people every year and kills up to one million, mostly children in sub-Saharan Africa. The high fevers, shaking chills, flu-like symptoms, and anemia can be fatal unless treated quickly. Malaria has grown resistant to a long list of drugs, and vaccines are still in experimental stages.
Working with the malaria parasite and human blood in test tubes and lab dishes, the research team identified a single fast-acting protein in the parasite that enables it and several dozen of its offspring to escape from a human red blood cell in preparation for quick invasion of many more healthy blood cells. Eliminating that protein traps the parasites in the cell.
After an infected mosquito bites a person, malaria parasites move into the liver, where they silently mature and multiply within weeks. Malaria parasites make people sick weeks or months later when they enter red blood cells and begin an exponential expansion. In a single cell, a parasite produces up to 32 offspring in about two days, which burst out to infect more red blood cells.
"This is the stage where things have to happen very fast for the parasite," said senior author Manoj Duraisingh, HSPH assistant professor of immunology and infectious diseases and senior author of the paper in the May 14 Science. "The parasite doesn't like to spend much time outside the cell. It grows and matures, and immediately following rupture, enters a new cell. It was a surprise that this protein kinase, which we thought would be involved in red blood cell invasion, turns out to be essential for the parasite getting out of the cell."
The study helps define the exit of the parasite from a blood cell as a highly choreographed process and distinguishes the egress and invasion steps, the researchers said.
"When the parasite gets out of the red blood cell, it has a matter of seconds or minutes to get into new red blood cells, or it will be cleared or killed by the human immune system," said first author Jeffrey Dvorin, a postdoctoral research fellow in the Duraisingh Lab at HSPH and a clinical fellow in pediatric infectious diseases at Children's Hospital Boston. "We found an important trigger for the parasite to exit cells that may be independent from the invasion trigger
http://www.sciencedaily.com/releases/2010/05/100514171912.htm
Subscribe to:
Posts (Atom)
