MALARIA: New malaria drug better but not cheaper

JOHANNESBURG, 21 April 2011 (IRIN)

 Photo: Ashley Clements/Flickr
Quinine takes four hours to be administered through an IV drip

The World Health Organization (WHO) this week recommended a change in the first-line treatment for malaria that could save nearly 200,000 lives a year, but health activists in Africa are bracing themselves for a potentially long battle in getting the new guidelines implemented.
Most cases of malaria are uncomplicated and non-fatal, particularly when patients have been exposed to the parasite and developed an immune response to it, but about eight million cases a year progress to “severe” malaria, which resulted in 781,000 deaths in 2009. Ninety percent of those occurred in Africa, where the disease is the leading cause of death in children.
Quinine has been the drug of choice for treating severe malaria for years, but it is difficult to administer and can have dangerous side effects.
"It requires a lot of calculation," said Veronique De Clerk, medical coordinator for international NGO, Médecins Sans Frontières in the northern Ugandan district of Kaabong. "You need to dilute it into infusions, and those infusions need to run through an IV [intravenous line] for four hours [every eight hours], and you need to monitor that, so it requires well-qualified personnel."
In rural Africa, where health workers are in short supply, it was common for patients to receive too much or too little quinine, with results that could be deadly, said De Clerk. "Recently, some studies from Uganda showed one in four administrations of quinine weren't correct."
WHO has recommended artesunate for severe malaria in adults since 2006, but this week revised its guidelines to include children, based on findings from a nine-country trial in Africa in 2010, which found that for every 41 children treated with artesunate instead of quinine, one life could be saved.
"It's very rare you have such a clear benefit of one drug over another, especially in neglected diseases like malaria," commented Nathan Ford, medical coordinator for MSF's Campaign for Access to Essential Medicines.
Several large clinical trials in the last decade have demonstrated that artesunate is safer, easier to use and more effective than quinine. It can be administered over three days either intravenously or through a daily intramuscular injection, meaning that non-medical personnel could be trained to provide the drug, bringing life-saving treatment closer to remote, rural communities.
It's very rare you have such a clear benefit of one drug over another, especially in neglected diseases like malaria
This week, MSF released a report, Making the Switch, which lists the benefits of treatment with artesunate rather than quinine, and the challenges in translating this evidence into policy and practice.
The biggest barrier is that artesunate costs two or three times more than quinine - around US$3.30 to treat one child compared to $1.3 for quinine - with additional costs for training health workers to administer it.
"Any change in protocol which results in an increase in cost is going to be a challenge in countries where health budgets are over-stretched," Ford told IRIN. MSF put the additional annual cost of treating severe malaria globally with artesunate at $31 million.
Ford said international donors could absorb this amount fairly easily, but had not traditionally supported the cost of treating severe malaria and would be unlikely to offer support until governments took the lead by changing their national guidelines.
"The WHO guidelines are just the first step," he told IRIN. "[They] need to be translated into national and local guidelines and protocols, with adequate training."
WHO recommended abandoning the use of chloroqine as the standard treatment for malaria a decade ago, but health professionals in some African countries still prescribe it. "It's a matter of changing long-term habits and practices," Ford commented.
De Clerk noted that although Uganda's national guidelines listed artesunate as an alternative to quinine, in reality the drug was unavailable. "For government, the price is important, and quinine has a very long shelf-life, so they'd want to get rid of those stocks first," she said.
WHO has prequalified only one manufacturer to produce artesunate, but MSF hoped that rising demand would encourage more manufacturers to enter the market, improving supply and reducing the price, and making long-term donor support unnecessary.
In the meantime, said Ford, "what we want is a very clear message from donors to say that any country switching [to artesunate] will be supported by us to cover the increased costs in the short term."
http://www.irinnews.org/report.aspx?reportID=92551

MALARIA: Antimalarial Trees in East Africa Threatened with Extinction

NAIROBI 21 April 2011

Scientists call for more research, conservation of trees to harvest potential for next generation of malaria drugs
Research released in anticipation of World Malaria Day finds that plants in East Africa with promising antimalarial qualities—ones that have treated malaria symptoms in the region’s communities for hundreds of years—are at risk of extinction. Scientists fear that these natural remedial qualities, and thus their potential to become a widespread treatment for malaria, could be lost forever.
A new book by researchers at the World Agroforestry Centre (ICRAF) and the Kenya Medical Research Institute (KEMRI), Common Antimalarial Trees and Shrubs of East Africa, provides a detailed assessment of 22 of the region’s malaria-fighting trees and shrubs. While over a thousand plant species have been identified by traditional healers as effective in the prevention or treatment of malaria symptoms, the species in the book were assigned by both traditional medicinal practitioners and scientists as those that have potential for further study.
According to researchers, many species of trees in East Africa are at high risk of extinction due to deforestation and over-exploitation for medicinal uses. Scientists in the field have been able to identify at-risk tree species, including those that have antimalarial qualities, by monitoring deforestation in the region and by talking to herbalists and local communities. According to researchers, not all species of antimalarial trees are at risk, particularly those that grow wild in lowland and coastal areas.
ICRAF is doing its part preserving these trees and shrubs by holding samples of most of the species with antimalarial qualities in its genebank and growing these trees in plant nurseries at its headquarters in Nairobi. The ICRAF genebank holds close to 200 species, of which at least 30 are known to have antimalarial properties.
The field data was gathered by ICRAF scientists conducting research across Kenya, Uganda, and Tanzania, where they met with approximately 180 herbalists and 100 malaria patients in 30 separate communities. KEMRI supported the process by supplying the information about each plant’s chemical compound make-up—research that is the result of a sophisticated laboratory process developed by KEMRI for testing natural products.
“We’ve only scratched the surface on the potential value of these plants. Although widely used by farmers and people in rural communities, most of this information has never been collected in a comprehensive way by researchers,” said Dr. Geoffrey Rukunga, Director of KEMRI’s Centre for Traditional Medicine and Drug Research and one of the book’s co-authors. “Going forward, I’d like to see more investment and more research on the power of these plants to fight the scourge of malaria and other diseases.”
One of the drugs most widely used historically to treat malaria, quinine, was derived from the bark of the Cinchona tree in South America. Today, the world’s newest, most-effective therapeutic treatment for malaria also comes from a plant, the Artemisia annua shrub. However, access to malaria therapies based on artemisinin compounds remains low—around 15 percent in most parts of Africa and well below the World Health Organizations’ 80 percent target.
Additionally, the malaria parasite’s ability to resist artemisinin is already beginning to emerge in Southeast Asia. This comes years after the World Health Organization labeled the spreading resistance of malaria to cheap and widely available drugs such as chloroquine and sulfadoxine-pyrimethamine as a major public health problem. The increasing failure of once-effective malaria drugs has added urgency to the search for promising new targets.
Malaria still kills some 800,000 people per year, the majority of whom are children under five years of age in sub-Saharan Africa. A lack of access to doctors and drugs leaves many communities in Africa with few alternatives other than looking for natural remedies to address symptoms of malaria, including high fever, severe headaches, bone aches, nausea and vomiting.
“We’re not saying that using these medicinal plants is a replacement for common prevention treatments like bed nets or effective medicines like ACT,” said Dr Najma Dharani, a Consultant Research Scientist at the ICRAF in Nairobi, Kenya, who led the field research portion of the study. “But we believe that it’s worth learning from communities that have been treating malaria symptoms with plants for hundreds of years. We need to do more research because one of these plants could prove to be the next Artemisia, and we need to do our best to preserve the plants that are going extinct.”
Indeed, without clear research or proper guidance for their sustainable use, many of the plants with medicinal properties are being over-exploited and are in danger of extinction. One such plant, which is critically endangered in Kenya and threatened in other regions, is Zanthoxylum chalybeum, commonly known as “Knobwood.” It grows in dry woodlands or grasslands of eastern and southern Africa and has been found to have antimalarial properties that need to be further explored. An extraction process from leaves, bark or root is used to effectively treat a malarial fever in many communities. Other uses for the plant include infusing tea with the leaves, making toothbrushes, and using the seeds as beads in traditional garments.
The African wild olive (Olea europaea Africana), also threatened in East Africa due to over-exploited for timber, contains organic extracts with significant levels of antimalarial activity, and is used to treat malarial and other fevers. The plant also acts as a natural laxative to expel parasites or tapeworms.
“Throughout my eight years of research in Africa, I have seen that we have an entire pharmacy in our farms and in our forests. We have plants that should be used by scientific companies to develop more options for malaria drugs,” said Dr. Dharan. “And we cannot become complacent and rely on one herb, because we’ve learned that developing resistance is likely.”
Beyond the complicated process to extract and test antimalarial compounds from these trees, scientists have struggled to track or replicate the treatment process as it occurs in communities. Besides the plant itself, there may be other factors contributing to a malaria patient’s recovery. For example, a healer may combine one plant with another that changes its chemical compound and boosts its effectiveness. Unless more is done to understand these processes in the field, scientists in laboratories and researchers at major drug companies will lose that knowledge.
“While we’ve made scientific progress identifying these compounds over the last few years, the fact is that we may lose these important trees before we’ve had a chance to understand their ability to defend us against malaria, a disease that devastates Africa—killing hundreds of thousands of our children and costing us billions of dollars in productivity year after year,” said Dr. Rukunga. “We need to approach this as an opportunity on multiple fronts: to preserve the biodiversity that may hold the next cure, to strengthen the research done on the ground in communities, and to continue our diligent work testing our natural resources in the lab.”

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The World Agroforestry Centre (ICRAF) is an autonomous, non-profit research organisation whose vision is a rural transformation in the developing world resulting in a massive increase in the use of trees in rural landscape by smallholder households for improved food security, nutrition, income, health, shelter, energy and environmental sustainability. The Centre generates science-based knowledge about the diverse roles that trees play in agricultural landscapes, and uses its research to advance policies and practices that benefit the poor and the environment. We are one of the 15 centres of the Consultative Group on International Agricultural Research (the CGIAR). http://www.worldagroforestrycentre.org/

The Kenya Medical Research Institute (KEMRI) was established in 1979 as the national body responsible for carrying out health science research in Kenya. Since then, KEMRI has served as a centre of excellence for health research in Africa. It works closely with the Kenyan Ministry of Health and various national councils and committees on issues of policy and priorities. The institute accomplishes its mandate through research centres that are intended to focus on certain specific areas of national and/or strategic importance. The centre that conducts research on herbal medicines is the Centre for Traditional Medicine and Drug Research (CTMDR). This centre studies the chemical composition, efficacy and safety of traditional medicines, and the socio-cultural and anthropological basis of the use of herbal remedies. http://www.kemri.org/

MALARIA: Chemotherapy drugs may be breakthrough in fight against malaria

Apr 19, 2011
Brussels - European researchers have found that chemotherapy drugs used to treat cancer also kill the parasite that causes malaria, in what the European Commission on Tuesday hailed as a breakthrough in the fight against the deadly mosquito-borne disease.
'This discovery could lead to an effective anti-malaria treatment that would save millions of lives and transform countless others,' the European Union's research commissioner, Maire Geoghegan-Quinn, said in a statement.
The research was led by EU-funded laboratories in Britain, France and Switzerland. They found that the malaria's plasmodium parasite 'hijacks' enzymes in human cells to multiply and that it can be stopped from doing so with chemotherapy drugs.
Scientists believe that the discovery will open the door to making cells inhospitable for plasmodium, rather than attacking the parasite directly - an approach that has been hampered by the plasmodium's ability to quickly become drug resistant.
'This strategy deprives the parasite of a major modus operandi for development of drug resistance,' the commission said.
The World Health Organization had warned in January that the world risked 'losing its most potent treatment for malaria' because of drug-resistant parasites, as some have already been found on the border between Cambodia and Thailand.
Although chemotherapy drugs come with notorious side effects, they are expected to be less acute in the case of malaria because of its shorter treatment period.
How to best use the drugs against malaria will now be tested in clinical trials, before researchers seek authorization to make them available worldwide for treatment of the disease.
The world is set to mark its annual Malaria Day on April 25. According to the WHO, the disease in 2009 infected some 225 million people, killing nearly 800,000.
It was the leading killer of children under 5 years old and infants in Africa, even though it is treatable.
'The ultimate goal is the complete eradication of the global scourge of malaria,' Geoghegan-Quinn said. 'Collaborative work across many borders is the only way of confronting such global challenges effectively.'
http://www.monstersandcritics.com/news/health/news/article_1633984.php/EU-Chemotherapy-drugs-may-be-breakthrough-in-fight-against-malaria

MALARIA: Urban malaria: myth and reality

Professor William Brieger discusses the common confusions in dealing with febrile illnesses in urban settings


Assume that you are a general practitioner or a staff nurse in a clinic or health centre in the crowded
Mushin area of Lagos, Nigeria. You are discussing with a 34-year-old male patient who is complaining of fever and body aches. He tells you he has ‘malaria’.
He has no history of travelling out to his home village in the past few months. You have heard that there
is not much malaria in Lagos, but you know there are big mosquitoes, and the most common complaint
among your clients is ‘malaria’. There are a variety of malaria drugs in your pharmacy, and from experience you know your clients will be happy if you prescribe one of the cheaper, older brands for them.
You decide that’s the easiest road to take … but is it the correct one?
http://www.africa-health.com/articles/january_2011/Malaria.pdf

MALARIA: Impact of national malaria control scale-up programmes in Africa: magnitude and attribution of effects

Richard W Steketee and Carlos C Campbell
Malaria Control and Evaluation Partnership in Africa
Malaria Journal 2010, 9:299doi:10.1186/1475-2875-9-299
27 October 2010
Background
Since 2005, malaria control scale-up has progressed in many African countries. Controlled studies of insecticide-treated mosquito nets (ITNs), indoor residual spraying (IRS), intermittent preventive treatment during pregnancy (IPTp) and malaria case management suggested that when incorporated into national programmes a dramatic health impact, likely more than a 20% decrease in all-cause childhood mortality, was possible. To assess the extent to which national malaria programmes are achieving impact the authors reviewed African country programme data available through 2009.
Methods
National survey data, published literature, and organization or country reports produced during 2000-2009 were reviewed to assess available malaria financing, intervention delivery, household or target population coverage, and reported health benefits including infection, illness, severe anaemia, and death.
Results
By the end of 2009, reports were available for ITN household ownership (n = 34) and IPTp use (n = 27) in malaria-endemic countries in Africa, with at least two estimates (pre-2005 and post-2005 intervals). Information linking IRS and case management coverage to impact were more limited. There was generally at least a three-fold increase in household ITN ownership across these countries between pre-2005 (median of 2.4% of households with at least one ITN) and post-2005 (median of 32.5% of households with at least one ITN). Ten countries had temporal data to assess programme impact, and all reported progress on at least one impact indicator (typically on mortality); in under-five year mortality rates most observed a decline of more than 20%. The causal relationship between malaria programme scale-up and reduced child illness and mortality rates is supported by biologic plausibility including mortality declines consistent with experience from intervention efficacy trials, consistency of findings across multiple countries and different epidemiologic settings, and temporal congruity where morbidity and mortality declines have been documented in the 18 to 36 months following intervention scale-up.
Conclusions
Several factors potentially have contributed to recent health improvement in African countries, but there is substantial evidence that achieving high malaria control intervention coverage, especially with ITNs and targeted IRS, has been the leading contributor to reduced child mortality. The documented impact provides the evidence required to support a global commitment to the expansion and long-term investment in malaria control to sustain and increase the health impact that malaria control is producing in Africa.
http://www.malariajournal.com/content/9/1/299

MALARIA: rectal treatment route for pre-referral emergency malaria treatment

Knowledge and acceptability of the rectal treatment route in Laos and its application for pre-referral emergency malaria treatment
Southisouk Inthavilay , Thierry Franchard , Yang Meimei , Elizabeth A Ashley and Hubert Barennes
Malaria Journal 2010, 9:342doi:10.1186/1475-2875-9-342
Published: 27 November 2010

Background
Rectal artesunate has been shown to reduce death and disability from severe malaria caused by delays in reaching facilities capable of providing appropriate treatment. Acceptability of this mode of drug delivery in Laos is not known. In 2009 the acceptability of rectal treatments was evaluated among the general Lao population and Lao doctors in a national survey.
Methods
A cross sectional survey was performed of 985 households selected through a multi-stage random sampling process from 85 villages in 12/18 provinces and of 315 health staff randomly selected at each administrative level.
Results
Out of 985 families, 9% had used the rectal route to treat children (the main indication was seizures or constipation). The population considered it less effective than other routes. Other concerns raised included pain (28%), discomfort for children (40%) and the possibility of other side effects (20%). Of 300 health staff surveyed (nurses 44%, doctors 66%), only 51% had already used the rectal route with a suppository, mostly to treat fever (76%). Health staff working in provincial hospitals had more experience of using the rectal route than those in urban areas. The majority (92%) were keen to use the rectal route to treat malaria although oral and intramuscular routes were preferred and considered to be more efficacious. Discussion and Conclusion Use of rectal treatments is uncommon in Laos and generally not considered to be very effective. This view is shared by the population and health care workers. More information and training are needed to convince the population and health staff of the efficacy and advantages of the rectal route for malaria treatment.
http://www.malariajournal.com/content/9/1/342