“Test and Treat” Model Offers New Strategy for Eliminating Malaria

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As researchers work to eliminate malaria worldwide, new strategies are needed to find and treat individuals who have malaria, but show no signs of the disease. The prevalence of asymptomatic or minimally symptomatic malaria can be as high as 35 percent in populations with malaria and these asymptomatic individuals can serve as a reservoir for spreading malaria even in areas where disease transmission has declined.

In a new study, researchers at the Johns Hopkins Malaria Research Institute found that a strategy of actively identifying undiagnosed malaria and then treating those with the disease resulted in significantly lower prevalence of malaria cases compared to a control group. Their findings are published in the February 3, 2012 edition of the journal PLoS ONE.

“New strategies are needed, particularly in areas of declining transmission. One strategy is to screen people for malaria and treat those who are infected, even those who are not sick enough to go to the clinic,” said lead author, Catherine G. Sutcliffe, PhD, an assistant scientist with the Johns Hopkins Bloomberg School of Public Health’s Department of Epidemiology. “Using artemisinin combination therapy can enhance this strategy, as treatment can reduce transmission to mosquitoes. In regions of declining transmission, the burden of malaria could be reduced to such an extent that elimination is achievable.”

The study was conducted in southern Zambia, with colleagues from the Johns Hopkins Malaria Research Institute in Macha. Researchers analyzed data from surveys conducted in 2007 and between 2008 and 2009. In both surveys, households were screened for malaria using rapid diagnostic tests and treated with artemisinin combination therapy when malaria was detected.

According to the new study, a proactive test-and-treat case-detection strategy resulted in a sixfold reduction in prevalence in 2008 and 2009, with the initial parasite prevalence at 4 percent. Test and treat showed a twofold reduction in 2007, when community prevalence was higher at 24 percent.

“Proactive case detection with treatment using artemisinin-combination therapy can reduce transmission and provide indirect protection to household members. If resources permit, this strategy could be targeted to hot spots to achieve further reductions in malaria transmission,” said William J. Moss, MD, senior author of the study and associate professor with the Johns Hopkins Bloomberg School of Public Health.

Worldwide, malaria afflicts more than 225 million people. The disease kills between 800,000 and 1 million people each year, many of whom are children living in Africa.

Authors of “Reduced Risk of Malaria Parastemia Following Household Screening and Treatment: A Cross-Sectional and Longitudinal Cohort Study” include Catherine G. Sutcliffe, PhD; Tamaki Kobayashi, PhD; Harry Hamapumbu; Timothy Shields, MA; Sungano Mharakurwa, PhD; Philip E. Thuma, MD; Thomas A. Louis, PhD; Gregory Glass, PhD; and William J. Moss, MD.

The Johns Hopkins Malaria Research Institute is a state-of-the-art research facility at the Johns Hopkins Bloomberg School of Public Health. It focuses on a broad program of basic science research to treat and control malaria, develop a vaccine and find new drug targets to prevent and cure this deadly disease.

The research was funded by the Johns Hopkins Malaria Research Institute.

Source: Johns Hopkins Bloomberg School of Public Health

Chloroquine side-effects

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QUESTION

For about two years in the early ’90s I indulged in self-prescription of chloroquine because then, I lived in a mosquito infested environment which made me suffer constant malarial attacks. Could this be why I now suffer from severe pains around my pelvis and down my thighs to one of my knées? I make this guess as a layman because recently, following a malarial attack, I took a non-chloroquine anti-malarial and discovered that the drug also provided me with temporary relief from those pains.

ANSWER

I have not found any information that suggests pelvic/leg pain could be one such effect. In fact, the only conclusive data is on irreversible retinal damage, which is a known consequence of long-term or high dosage chloroquine use. If you have experienced difficulty reading or other visual problems, it may be worth getting screened.

Since your symptoms improved with taking another anti-malarial, it may be that you have some other infection or illness which responds to the anti-malarial drugs (which are known to be effective against other diseases – for example, artemisinin can be used to treat schistosomiasis, a parasitic worm infection). This is something you should discuss with your doctor, as chronic pelvic pain can have a variety of causes and is often misdiagnosed.

Scientists Develop Method to Synthesize Artemisinin Inexpensively and in Large Quantities

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Prof. Dr. Peter H. Seeberger and Dr. François Lévesque. Copyright © MPI of Colloids and Interfaces

In future it should be possible to produce the best anti-malaria drug, artemisinin, more economically and in sufficient volumes for all patients.

The most effective anti-malaria drug can now be produced inexpensively and in large quantities. This means that it will be possible to provide medication for the 225 million malaria patients in developing countries at an affordable price.

Researchers at the Max Planck Institute of Colloids and Interfaces in Potsdam and the Freie Universität Berlin have developed a very simple process using oxygen and light for the synthesis of artemisinin, the active ingredient that pharmaceutical companies could only obtain from plants up to now. The chemists use a waste product from current artemisinin production as their starting substance. This substance can also be produced biotechnologically in yeast, which the scientists convert into the active ingredient using a simple yet very ingenious method.

There is an effective treatment against malaria, but it is not accessible to all of the more than 200 million people worldwide who are affected by the disease. Millions, especially in the developing world, cannot afford the combination drug preparation, which consists mainly of artemisinin. Moreover, the price for the medication varies, as this substance is isolated from sweet wormwood (Artemisia annua) which grows mainly in China and Vietnam, and varies seasonally in its availability.

To make the drug affordable for at least some patients in developing countries, the Clinton Foundation, for example, subsidises its cost to the tune of several million dollars per year. Nevertheless, over one million people die of malaria each year because they do not have access to effective drugs.

This may be about to change. Peter H. Seeberger, Director at the Max Planck Institute of Colloids and Interfaces in Potsdam and Professor of Chemistry at the Freie Universität Berlin and his colleague François Lévesque have discovered a very simple way of synthesising the artemisinin molecule, which is known as an anti-malaria drug from traditional Chinese medicine and has an extremely complex chemical structure. “The production of the drug is therefore no longer dependent on obtaining the active ingredient from plants,” says Peter Seeberger.

Synthesis from a by-product of artemisinin production

As a starting point, the chemists use artemisinic acid – a substance produced as a hitherto unused by-product from the isolation of artemisinin from sweet wormwood, which is produced in volumes ten times greater than the active ingredient itself. Moreover, artemisinic acid can easily be produced in genetically modified yeast as it has a much simpler structure.

“We convert the artemisinic acid into artemisinin in a single step,” says Peter Seeberger. “And we have developed a simple apparatus for this process, which enables the production of large volumes of the substance under very controlled conditions.” The only reaction sequence known up to now required several steps, following each of which the intermediate products had to be isolated laboriously—a method that was far too expensive to offer as a viable alternative to the production of the drug from plants.

The striking simplification of artemisinin synthesis required not only a keen sense for an elegant combination of the correct partial reactions to enable the process to take place in a single step; it also took a degree of courage, as the chemists departed from the paths typically taken by industry up to now. The effect of the molecule, which not only targets malaria but possibly also other infections and even breast cancer, is due to, among other things, a very reactive chemical group formed by two neighbouring oxygen atoms, which chemists refer to as an endoperoxide.

Peter Seeberger and François Lévesque use photochemistry to incorporate this structural element into the artemisinic acid. Ultraviolet light converts oxygen into a form that can react with molecules to form peroxides.

800 photoreactors should suffice to cover the global requirement for artemisinin

“Photochemistry is a simple and cost-effective method. However, the pharmaceutical industry has not used it to date because it was so difficult to control and implement on a large scale,” explains Peter Seeberger. In the large reaction vessels with which industrial manufacturers work, flashes of light do not penetrate deeply enough from outside and the reactive form of oxygen is not produced in sufficient volumes.

The Potsdam-based scientists have succeeded in resolving this problem using an ingenious trick: They channel the reaction mixture containing all of the required ingredients through a thin tube that they have wrapped around a UV lamp. In this structure, the light penetrates the entire reaction medium and triggers the chemical conversion process with optimum efficiency.

“The fact that we do not carry out the synthesis as a one-pot reaction in a single vessel, but in a continuous-flow reactor enables us to define the reaction conditions down to the last detail,” explains Peter Seeberger. After just four and a half minutes a solution flows out of the tube, in which 40 percent of the artemisinic acid has become artemisinin. “We assume that 800 of our simple photoreactors would suffice to cover the global requirement for artemisinin,” says Peter Seeberger.

And it could all happen very quickly. Peter Seeberger estimates that the innovative synthesis process could be ready for technical use in a matter of six months. This would alleviate the global shortage of artemisinin and exert considerable downward pressure on the price of the associated drugs.

Reference: François Lévesque and Peter H. Seeberger
“Continuous-Flow Synthesis of the Anti-Malaria Drug Artemisinin”
Angewandte Chemie international edition, 17. January 2012; DOI: 10.1002/anie.201107446

Source: Max Planck Institute of Colloids and Interfaces

Counterfeit Anitmalarial Drugs Threaten Crisis in Africa

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Hopes of at last controlling malaria in Africa could be dashed by the emergence of poor-quality and fraudulent antimalarial medicines, warn experts writing in Malaria Journal. Unless urgent action is taken both within Africa and internationally, they argue, millions of lives could be put at risk. [Read more…]

Treatment of Malaria in India

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QUESTION

In India how to treat a child and adult suffering from malaria?

ANSWER

Chloroquine-resistant malaria has been observed in India and so the first line drug of choice should be an artemisinin-derivative in combination with another drug (this group of medications are more generally known as “artemisinin-based combination therapies” or ACTs). A common example of this is artemether in combination with lumefantrine, which is marketed as Coartem. Coartem is also used to treat malaria in children over 11 pounds (5 kg) in weight.

Researchers Introduce Technology to Manufacture Artemisinin in Tobacco Plants

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Combating malaria is one of the eight Millennium Development Goals described in the United Nations Millennium Declaration signed by all UN members at the year 2000. A key intervention to control malaria is prompt and effective treatment with artemisinin-based combination therapies. Artemisinin is a natural compound from Artemisia annua (sweet wormwood) plants, but low-cost artemisinin-based drugs are lacking because of the high cost of obtaining the natural or chemically synthesized drug. Despite extensive efforts invested in the last decade in metabolic engineering of the drug in both microbial and heterologous plant systems, production of artemisinin itself was never achieved.

Recently, Yissum Research Development Company of the Hebrew University of Jerusalem Ltd., the technology transfer arm of the University of Jerusalem, introduces a novel method allowing artemisinin production in a heterologous (that is, other than A. annua) plant system, such as tobacco. The method was developed by Professor Alexander Vainstein from the Robert H. Smith Faculty of Agriculture, Food and Environment at the Hebrew University, and sponsored by a fellowship of Mr. Isaac Kaye. It was published under the title “Generation of the Potent Anti-Malarial Drug Artemisinin in Tobacco” in the latest issue of the prestigious publication Nature Biotechnology.

Professor Vainstein and his graduate student Mr. Moran Farhi have developed genetically engineered tobacco plants carrying genes encoding the entire biochemical pathway necessary for producing artemisinin. In light of tobacco’s high biomass and rapid growth, this invention will enable a cheap production of large quantities of the drug, paving the way for the development of a sustainable plant-based platform for the commercial production of an anti-malarial drug. The invention is patented by Yissum, which is now seeking a partner for its further development.

Yaacov Michlin, CEO of Yissum said, “Professor Vainstein’s technology provides, for the first time, the opportunity for manufacturing affordable artemisinin by using tobacco plants. We hope that this invention will eventually help control this prevalent disease, for the benefit of many millions of people around the globe, and in particular in the developing world.”

Malaria is caused by a parasite called Plasmodium, which is transmitted via mosquitoes. Symptoms of malaria include fever, headache, and vomiting, and usually appear between 10 and 15 days after the mosquito bite. If not treated, malaria can quickly become life-threatening by disrupting the blood supply to vital organs.

More than 3 billion people are at risk of malaria. Every year, this leads to about 250 million malaria cases and nearly one million deaths. People living in the poorest countries are the most vulnerable.

Malaria is especially a serious problem in Africa, where 20% of childhood deaths are due to the effects of the disease and every 30 seconds a child dies from malaria.

Source: Business Wire

I am getting malaria every 6 months

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QUESTION:

I am getting malaria every six months, after taken chloroquine medicine tablets. Is this  normal,when my resistance is low, or is it coming aging, is there any medicine to clear the malaria?

ANSWER:

While taking chloroquine can be used to treat malaria, it will not prevent re-infection, unfortunately. One thing to check though is whether you are living in an area where the local types of malaria might be resistant to chloroquine; if so, it will be worth seeing if you can be treated with artemisinin-based combination therapies (ACTs), such as Coartem or Lonart, instead.

Again, these will not prevent re-infection, however, so you need to also take other preventative actions, such as sleeping under a long-lasting insecticide treated bednet and wearing long-sleeved clothing in the evenings and at night to prevent mosquito bites.

It sounds from your question like you live in an area where malaria is common; however, if you are actually only travelling to malarial areas regularly, you could also ask your doctor about the possibility of taking preventative medicine against malaria for the time that you are travelling (these are called “prophylactics”).

You should also check which species of malaria parasite you are infected with – this can be determined when you are diagnosed with the infection, either through looking at your blood under a microscope or by using a rapid diagnostic test (RDT). If you Plasmodium ovale or Plasmodium vivax, there is a possibility that even though the initial acute phase of the infection is responding to treatment with chloroquine, the parasite is remaining dormant in your liver, and causing the recurrences every 6 months. In this case, you should ask your doctor about the possibility of taking a drug called primaquine, which kills these liver stages and prevents further relapse of the disease.

Causes of malaria, treatment with drugs and emerging resistance

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QUESTION:

What is malaria and what causes it besides bacteria? What is the name of the causal agent for malaria, which drug is used to cure it and how do the pathogens become resistant to the drugs?

ANSWER:

There are many questions in there! Malaria is actually caused by a single-celled animal, called a protozoan; it’s not a bacterial disease. There are different species of these protozoans, which form a genus called Plasmodium; the different species cause different types of malaria, for example Plasmodium falciparum, the most deadly and severe form, and Plasmodium vivax, which is widespread throughout the world but is a less acute infection. These different forms of malaria are each treated with different medications, depending on what is most effective and available; P. vivax, for example, can be treated with chloroquine, whereas in many places, P. falciparum has become resistant to this drug. In areas where resistance to chloroquine has emerged, other drugs are used; in Africa, artemisinin-based combination therapies (ACTs) are commonly used against chloroquine-resistant P. falciparum. Other drugs used to treat malaria include quinine compounds such as quinine sulphate, mefloquine, sulfadoxine-pyrimethamine and medications combining proguanil with atovaquone (marketed as Malarone).

The emergence of resistance to these drugs is a worrying phenomenon with respect to malaria; it is such a widespread and deadly disease, that the consequences of failed treatment are very high. Resistance can be caused by many factors, at the level of the drug, the human host, the mosquito host and also the malaria parasite itself. For example, poor drug compliance during treatment can lead to a failure to clear an infection completely, allowing the remaining parasites, which were less susceptible to the drug, to survive and reproduce. With successive generations, natural selection will lead to the evolution of strains of malaria parasites which are firmly resistant to that drug. The same process occurs when mass drug administration programmes, for example in areas of high malaria endemicity, give people sub-therapeutic doses of medication (in other words, doses of the drug that are too low to kill the parasite). Another problem is when people are not checked for their infection status after having been treated for malaria; if treatment fails for some reason, they will still have parasites in their blood, and should be treated again to ensure that all the malaria has been killed. If this doesn’t happen, the parasites can carry on reproducing, as in the processes described above. For these reasons, it is crucially important for people to be given accurate doses of medication, to ensure that they complete the full course of treatment, and that once treatment has been completed, they are accurately tested as negative for the malaria parasite. Finally, there are factors related to the affinity of the malaria parasite to its vector mosquito hosts which can lead to the emergence of drug resistant strains. For example, it has been shown that strains of malaria which are resistant to chloroquine are better able to survive and reproduce inside their mosquito hosts, leading to a greater population size of resistant parasites compared to drug-susceptible ones. It is for these reasons that malaria treatment and control programmes are now being very careful with the ways in which they administer drugs and monitor infections, in order to limit any further reisstance developing; similarly, pharmaceutical and biochemical researchers are constantly on the look-out for new compounds or methods of killing malaria parasites, which can be developed into new forms of treatment.

In which country did malaria start?

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QUESTION:

In which country did malaria start?

ANSWER:

That’s an interesting question! In terms of the evolution of the disease, the different types of malaria probably evolved in different places; it is hypothesised for example, that P. falciparum evolved from a related strain of malaria that is found in gorillas in central Africa, so the human form also probably originates from that area. Although an exact date for the origin of P. falciparum is still under debate, it was probably sometime around 10,000 years ago,  long before modern countries existed in the region!

As for when malaria was first recorded in human populations, it was known in ancient China, as long ago as 2700 BCE, when the ancient Chinese medical text, Nei Ching, was written. Two and a half thousand years later, in around 200 BCE, there are descriptions of the use of Artemisia annua for the treatment of malarial-type fevers; extracts from this plant, known as artemisinins, are still used for the treatment of malaria today.

Malaria was also known from Europe by the 4th century BCE when it was described by ancient Greek writers. The Romans too were aware of malaria and the risks it posed; they even associated the disease with stagnant water (required by mosquitoes to breed, though it is unclear whether they actively understood the association between mosquito bites and the fevers), which led to extensive public drainage works in order to eliminate bodies of standing water.

Given the lack of written histories, it is more difficult to determine the earliest understanding of malaria in the Americas. However, when the Spanish arrived in the 15th century, they learned of local remedies that the indigenous populations had for various fevers; one of these natural medicines was the bark of a tree of the genus Chichona. More commonly called quinine, this compound is still used as an anti-malarial in modern times.

Nowadays, vector control measures, efficient health monitoring systems and treatment availability has much reduced and in some cases even eradicated the transmission of malaria from most of the United States, Europe and even large parts of China. The greatest burden of the disease continues to be in the tropical regions of the world, and in particular, in sub-Saharan Africa.

Malaria-Fighting Plants Under Threat

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Researchers warn that East African plants that could cure malaria could disappear before scientists have a chance to study them.

The World Health Organization estimates 800,000 people die of malaria each year, most of them young children in Africa.

A new book by scientists at the World Agroforestry Centre, “Common Antimalarial Trees and Shrubs of East Africa,” identifies 22 tree and shrub species that traditional healers in East Africa use to fight the disease.

But, the researchers say, they are being cut down for cooking fuel and other uses and could disappear before scientists have a chance to study them.

For example, the threatened African wild olive, Olea africana, has anti-malarial properties that scientists say deserve further study.

Herbal medicine

A person suffering from malaria in East Africa is likely to visit a local herbalist for treatment. Lead author Najma Dharani at the World Agroforestry Center in Kenya says the traditional healer may recommend the patient take a few grams of a plant known locally as knobwood.

Either root or bark may be used, fresh or as powder. “It’s quite bitter,” she says. “Drink it for three or four days, until it cures a person.”

Dharani and her colleagues at the Kenya Medical Research Institute have used modern science to identify promising malaria-fighting compounds in knobwood and 21 other trees and shrubs native to the region.

Traditional cures at risk

She has spent the last 12 years studying medicinal plants in East Africa with the potential to treat a range of diseases. A lot more research is needed to identify how effective they are and how they work, but she notes that they have been used by traditional healers for centuries.

“This is not today’s knowledge,” she says. “This is very old knowledge, indigenous knowledge, which has been disappearing because the youngsters don’t take it (up).”

The knowledge is not all that’s disappearing. Dharani says the some of these anti-malarial trees and shrubs are being cut down at an alarming pace, along with other wood in the area, largely to make charcoal. That’s the cooking fuel of choice for many poor people around the world who can’t afford other options.

Limited options for treatment

She understands the economic motivation to cut down the trees. But, she says, it will be these same poor people who will ultimately suffer.

“They don’t have access to clinics. They don’t have doctors,” she says. “They have to go hundreds of kilometers to reach clinics. So, it’s so very important for local communities to conserve these trees. If [the trees] completely vanish, they will remain with nothing.”

The World Agroforestry Center is working to reduce deforestation by encouraging people to grow their own trees for timber or firewood, rather than harvesting the forest. The center also is helping communities plant medicinal trees and shrubs, and conserving samples of the trees in its genebanks and nurseries.

Knobwood extract would not be the first plant to cure malaria. The first anti-malarial drug, quinine, came from the bark of a South American tree. The latest treatment, artemisinin, comes from a Chinese shrub. The next cure could come from East Africa — but not if the last tree is burned up as charcoal.

Source: VOA News