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Drug resistance due to parasite mutation was a key driver of malaria’s resurgence in sub-

Saharan Africa in the 1990s. Southeast Asian countries demonstrated the efficacy of a new but expensive treatment and, together with a Swiss pharmaceutical company, developed the first fixed-dose artemisinin-based combination therapy (ACT) for malaria. Few countries claimed they could afford to adopt this drug as a first line treatment. Advocates, malaria scientists and United States Congress ultimately exposed the folly of continuing to fund outdated drugs like chloroquine and sulfadoxine-pyrimethamine (SP), and donor agencies moved to meet the huge need for ACTs.

The results have been a mixture of success and systemic failure. The United States Government, World Bank and the Global Fund to Fight AIDS, TB and Malaria have substantially increased malaria control funding and through the World Health Organisation (WHO) and Roll Back Malaria Partnership (RBM) provided technical assistance to help countries change treatment guidelines to ACTs and devise strategies to finance them. As of September 2007, ACTs are listed as first-line treatments for uncomplicated malaria in every national treatment policy in sub-Saharan Africa where they are needed. The Global Fund is helping to deliver 264 million ACTs, backed by an unprecedented $471 million allocation for malaria control (42% of total allocations) in its most recent round of grants (Round 7). Largely as a result of these efforts, some African countries are reporting localized declines in malaria cases and deaths.

Yet the rising demand for artemisinin has increased incentives for producers to market

artemisinin as a monotherapy. The WHO has explicitly recommended against this practice, as widespread exposure could accelerate parasite resistance to artemisinin. No new class of antimalarial treatment is expected to enter the market for at least a decade, so all foreseeable malaria treatment strategies depend on the integrity of this drug. Recent evidence from Southeast Asia suggests that artemisinin may be losing effectiveness against malaria. If this is attributable to parasite resistance, Africa may not be far behind.

Unfortunately, public health systems on the African continent remain weak and underdeveloped. Most people still seek treatment from the private sector, where substandard and artemisinin monotherapy drugs abound. Africa Fighting Malaria (AFM) has confirmed this in a recent study of private sector antimalarial drug quality in six African countries: Ghana, Kenya, Nigeria, Rwanda, Tanzania and Uganda. Antimalarial monotherapy tablets, including artemisinin, were widely available in urban and peri-urban pharmacies, with 35 percent of all treatments failing basic content testing.

This comes as no surprise. Only 20 percent of the WHO’s 191 member states currently have well-developed drug regulation. Post-market surveillance of the private sector in low-income countries is practically non-existent, and national drug registries are infrequently updated or publicized. Africa has only six WHO-registered national pharmacovigilance systems to detect substandard drugs. Though the agency has made efforts to scale these up and develop new sites, resistance monitoring networks remain severely limited.

In the absence of strong national regulatory and pharmacovigilance systems, consistent leadership among donor agencies providing ACTs is critical and sorely lacking. The Global

Fund has adopted a stand-alone policy of procuring drugs not tested by competent agencies. This is intended to increase competition and spur price reductions, but it may result in the distribution of unsafe drugs. Such practice is forbidden in developed countries. The Executive Director of RBM has voiced concerns about the quality of these drugs, but the Global Fund is reticent to leave nascent copy drug companies in the lurch.

An outgrowth of the trend toward generics and copy drugs is local production of pharmaceuticals. Some donors aggressively advocate this concept even as they acknowledge safety risks and substantial opportunity costs. Tremendous investment of limited resources will be required to turn African factories into viable, internationally-accredited production facilities.

Further, localized producers have an inclination and incentive to protect their output by lobbying for tariffs and other protective measures, which threaten to increase costs and impede access to quality drugs. Ideological support for local production destructively conflates industrial and public health policy, and provides copy drug companies little incentive to improve quality. The latter point is most concerning as donor agencies roll out new treatment solutions like the Affordable Medicines Facility malaria (AMFm). If approved, this initiative will adopt the commendable goal of subsidizing ACTs for private and public sector distribution.

Unfortunately it plans to compromise on drug quality standards in line with the Global Fund. Without a commensurate strengthening of national regulation, postmarket surveillance and

pharmacovigilance to pace the inevitable development of artemisinin resistance, such policies could result in setbacks for malaria control and public health.

Substandard drugs continue to circulate in Africa, causing an estimated 200,000 avoidable deaths from malaria alone each year. Structural reforms are elusive. Malaria endemic countries remain hugely dependent on donors, who too often reward policy failures with new aid initiatives. Eight years ago, African governments pledged to remove taxes and tariffs on malaria control technologies, and devote at least 15 percent of their national budgets to improving health care. Most are failing to live up to these commitments. Unless Africa takes its own health care more seriously, the present gains against malaria should not be expected to last.

The solution to the malaria problem in Africa lies in engaging local people to find out what they know about malaria and what they are capable of doing in order to control the disease.

Kenya is one of the countries that have the best knowledge about malaria in the world today. Paradoxically, it is also one of the countries with the highest number of people who succumb to the disease.

This shows that African countries have not laid out proper strategies on how to fight the disease, and they have not fully participated in the control of the disease. First, the solution to the malaria problem in Africa lies in engaging local people to find out what they know about the disease and what they are capable of doing in order to control it.  This information can then be used to develop products and services that are relevant to the needs of African people.

The global health agencies concerned with malaria control must focus on understanding how people control, treat and the beliefs on malaria locally, instead of bringing solutions imposed from the West. The problem is that the West has owned the malaria problem, and continues to leave Africans out when seeking solutions.

Malaria is a major killer disease in Africa. The World Health Organisation (WHO) reported that about 1.3 million people died from the disease in 2005. Children and pregnant women are more susceptible to malaria. About 90 per cent of malaria deaths occur in children under five years of age.

The health body recommends widespread use of treated mosquito nets, and spraying of insecticides around houses, arguing that sleeping under the mosquito nets reduces the likelihood of catching malaria by about 25 per cent.

This was the argument that was used to create the Roll Back Malaria Programme in 1998, with an aim of reducing malaria prevalence by 50 per cent every five years.  In 1998, malaria killed only about 250,000 people each year worldwide. The plan by WHO was a massive distribution of millions of insecticide treated mosquito nets throughout the continent and other areas in of the world where malaria is endemic. These were good intentions. 

The programme  only worked on one front. The organisation managed to distribute millions of insecticide treated nets in many African countries. But malaria cases did not reduce. In fact, since 1998, the number of deaths due to malaria have steadily risen from 250,000 to 1.3 million deaths by 2005.

Analysts have offered explanations to this increase in the face of increased investment to fight the disease. One of the explanations was that the people living in malaria endemic zones did not use the mosquito nets as advised.

Other said people living in malaria endemic areas used the mosquito nets exactly as WHO recommended, but the mosquitoes bit them before they went to bed. Thus, the people are likely to have contracted malaria already before using the treated nets.

According to the recommendation WHO, the nets are only used when sleeping. This hinders the purpose of use of nets as a way to eradicating malaria because people do not carry the net everywhere.

The mosquitoes come out in the evenings and these are times when women are preparing food in open places, young children are winding up the play time before dinner. At this time, the mosquitoes are busy buzzing around, looking for candidates to bite.

They bite unsuspecting pregnant women sitting at the fireplace and the children playing outside. By the time they go to bed under the care of treated nets the bite from the mosquito has already transmitted the malaria parasites. In these circumstances, bed nets do not offer any protection. 

The bed nets recommended by WHO are treated with pyrethroids. A pyrethroid is a synthetic version of natural pyrethrin. The WHO imports pyrethroids from a Japanese manufacturer, to treat mosquito nets imported from China. The pyrethroids are also used for indoor residual spraying.

Why does WHO import pyrethroids to Kenya instead of buying pyrethrum from Kenyan farmers? Why do they have to import the nets when they can buy them from a local manufacturer?

 The fundamental problem is that this leads to flooding of synthetic pyrethroid in the local market. This story is not unique to Kenya. The same thing is happening in Tanzania, Uganda, Rwanda and Burundi. 

It is time for Kenyan pyrethrum producers to get involved in malaria control. First they will contribute to eradicating a disease that is killing millions of Africans, and second, they will generate new and sustainable sources of income. Kenyans have grown pyrethrum for many years. However, Kenyans do not grow pyrethrum for malaria control. Pyrethrum Board of Kenya (PBK) exports most of the pyrethrum produced in Kenyan.

It is time that PBK markets the produce instead of the aggressive Japanese business reaping all the benefits.

If the PBK sold pyrethrum to WHO, pyrethrum farmers would benefit. This will also reduce the cost of the insecticides as they will be locally produced.  Kenyans should seize this opportunity and help fight malaria.

The business people can create a pyrethrum extraction plant and encourage increased production of pyrethrum in the Kenyan highlands.  Kenyan pyrethrum still has a very big demand internationally.

What about the nets? Kenyan business people should invest in mosquito net manufacturing . The local people should own the malaria business if we are to bring malaria under control. The protection of PBK to solely extract and market pyrethrum is unethical because the body does not invest in malaria control business.

The government must remove any remaining restrictions in the Pyrethrum Act impeding local people to engage freely in malaria control business. Foreign companies such as the Sumitomo of Japan and East African Botanicals, and Kenya Private Sector Alliance and similar business associations can work together to lobby the government to remove all clauses that restrict local people from participating in the entire value chain of pyrethrum products.

With appropriate government response and revisions of the Act , the next step is to build the system for increasing pyrethrum production.

Pyrethrum management is a low technology business and easily affordable. Traditionally, people used to harvest pyrethrum flowers and dry the flowers hanging upside down to increase pyrethrin concentration. Modern commercial production plants have high tech driers in aerated buildings. The aerated buildings are not necessary in Kenya where there is abundance of sunshine. The flowers dry well on drying racks under the sun.

The idea is to dry them until the moisture content reduces to about 10 per cent. The next step involves crushing the dry flowers into a fine powder. The fineness of the powder influences the pyrethrum efficiency and the longevity. Finer powder is more efficient in killing insects, but it loses the pyrethrin content much faster. A coarse powder is less efficient but lasts longer.

Crushing the stems with the flowers does not reduce the pyrethrin concentration.

The problem with pyrethrum extract is that it is very sensitive to light. When exposed to light, the extract can last up 10 days in a sealed container at room temperature. Dried extract can however last for up to six months when kept in the dark without refrigeration. Because of this sensitivity to light, it is wise to store the pyrethrum extract in amber coloured bottles.

The two ways of using pyrethrum are dusting or spraying. Cool temperatures enhance the insecticide effect of pyrethrum. Therefore, it is better to spray or dust in late afternoon. The sun also accelerates degradation.

Farmers use pyrethrum to protect their crops from parasites, by applying the crushed powder leaves of plants requiring protection. People burn the uncrushed dried flowers to repel and kill mosquitoes. Some people mix the crushed flowers with sawdust and burn them to chase mosquitoes.

This is the idea behind mosquito coils. Pyrethrin extract is also packaged as a spray. Though this is a more high tech end of production. Pyrethrin production  does not require a huge starting capital. Yet investment in pyrethrum business, or malaria control business is very lucrative with very huge returns. Other crops that Kenyans  can benefit from include Artemesia and neen.

They are many investment opportunities in other products discovered by our scientists at the universities, research institutions such as KEMRI, KARI, and ICIPE that Kenyans need to embrace. 

The writers are members of Knowledge Development Network

www.kdnc.org

Some 35% of antimalarial drugs sold in six major African cities failed basic quality tests according to a study published today in PLoS ONE, a peer-reviewed open-access journal.

The cities were in Ghana, Kenya, Nigeria Rwanda, Tanzania and Uganda. The study further found that artemisinin monotherapies, which the World Health Organisation explicitly rejects as substandard, remain common in Africa. Substandard antimalarial drugs cause an estimated 200,000 avoidable deaths each year.

"Our study shows that efforts to increase access to quality antimalarial drugs in Africa are increasingly important," said Dr. Roger Bate, Resident Fellow at the American Enterprise Institute and lead author on the study. "Substandard drugs not only endanger lives today, but also jeopardize future malaria treatment strategies by accelerating parasite resistance."

Artemisinin combination therapies, or ACTs, lower the chances of developing parasite resistance and reducing treatment efficacy. Yet a third of the drugs collected in the study were artemisinin monotherapies. 42% of them failed and 78% were manufactured after the World Health Organisation proscribed them in January 2006.

"Malaria surged through Africa in the 1990s, fueled by resistance to chloroquine and other historically effective drugs," said Richard Tren, Director of Africa Fighting Malaria, a non-profit advocacy group. "Because regulation and post-market surveillance of drugs is so poor in most malarial countries, ACTs now risk the same fate."

The World Health Assembly resolved in May 2007 to stop the production and marketing of artemisinin monotherapies. But according to the World Health Organisation, only 40 of 74 global manufacturers have agreed in principle to stop production, and 42 countries - 18 of them in sub-Saharan Africa - still allow companies to market these drugs.

Africa Fighting Malaria also released a report on malaria treatment policy in Africa today, available at: . The report examines the challenges of pharmaceutical regulation and production in Africa, and calls for stronger global leadership from donors on drug procurement standards.

"Under the Global Fund’s ’Option C’, poor countries can use taxpayer funds to buy untested drugs of uncertain quality," said Richard Tren. "Option C was intended to increase incentives for nascent ACT producers to enter the market and foster competition. It has accomplished this, but it has not provided any incentives for these companies to go the extra step and submit to bioequivalence testing by a stringent regulatory authority."

Post-market surveillance and pharmacovigilance are severely limited in Africa, yet crucial to detecting bad drugs and the inevitable development of parasite resistance for an at-risk population of 700 million. As the PLoS ONE study argues, a fraction of the current global budget for malaria control could support a decentralized network for basic drug quality testing in Africa using Minilabs, portable chemistry sets, or equivalent technologies.

A health warning: counterfeit medicines can do even greater damage than heroin and cocaine

Heroin and cocaine are not the only illegal drugs with a terrible impact on global health. Counterfeit medicines can do much greater damage.

Some of these fakes contain potentially toxic chemicals. Others are like homoeopathic remedies - while harmless in themselves, as they contain no active ingredients, they do not work as advertised. When taken to treat a potentially lethal disease, they can kill.

They are certainly killing in South-East Asia. Artesunate is one of the most effective drugs for treating malaria, and up to half the tablets on sale in the region are counterfeit. Most contain no artesunate at all. The acutely ill patients who use them, many of them children, are taking nothing stronger than a placebo, and thousands are dying as a result. Some fake antimalarials carry a secondary threat. They contain traces of artesunate too small to be clinically useful, but significant enough to encourage resistance to one of the few antimalarials that is still widely effective.

Traffic in counterfeits has traditionally been treated as minor fraud, but there have recently been welcome signs of change. An outstanding piece of scientific detective work, led by the Wellcome Trust and Interpol, has cracked one of the world’s worst counterfeiting rings. By analysing traces of pollen and environmental contaminants in fake artesunate, Operation Jupiter has tracked the origin of many batches to one region of China. Six arrests followed, along with the seizure of thousands of fake packets.

This was an important breakthrough, and there is already evidence that it has helped to stanch the flow. Targeting manufacturers, however, can be only part of the solution to this lethal trade. It exists for a simple reason: antimalarials are too expensive, which leaves a market niche for cheap knock-offs that criminal gangs will always find a way to exploit.

A project called the Affordable Medicines Facility for Malaria is seeking funding to subsidise accredited factories to produce effective drugs for developing countries. The Global Fund to Fight Aids, Tuberculosis and Malaria will soon decide whether to provide the $1.9 billion it needs over five years.

The provision of cheaper antimalarials, of course, would be a social good in itself. A positive ruling would also do far more to undermine counterfeiting than forensic science can hope to achieve.

The £80 million funding crisis in British physics - the subject of a damning select committee report last week - may be just the start of the field’s problems. One of the biggest slices of the physics budget is the UK’s subscriptions to international partnerships such as Cern, the European Space Agency and the European Southern Observatory, and these are all priced in euros. Unless the Government moves to guarantee these against the fluctuating value of the pound, further belt-tightening may soon be necessary.

London School of Hygiene & Tropical Medicine (University of London)
Department of Infectious and Tropical Diseases
Disease Control and Vector Biology Unit

Post of MIP Trial Coordinator, West Africa
Application deadline: 23 May 2008

Website: http://www.lshtm.ac.uk

An exciting and challenging opening is available for an epidemiologist, clinician or public health specialist to coordinate a large trial of intermittent preventive malaria treatment in the prevention of malaria in pregnancy (IPTp) that will be conducted in three to four countries in West Africa with support from a grant from the Malaria in Pregnancy Consortium. The objective of this trial is to determine whether in areas where malaria transmission is highly seasonal, a reduction can be made in the number of doses of intermittent preventative treatment needed or in the duration for which intermittent preventive treatment is given.

The primary responsibility of the coordinator will be to ensure that activities at the sites where the trial will be conducted are well integrated and conducted to a high standard. Each site will have its own project leader with responsibility for activities at that site.

Applicants, who may be clinically or non-clinically qualified, should have a post-graduate qualification in epidemiology or public health and experience of conducting clinical trials in a developing country.

Applicants must have excellent communication and management skills and some knowledge of French.

An appointment will be made as soon as possible. A contract of 36 months will be offered. The appointment will be made on the Clinical or Non-Clinical Lecturer scale with a starting salary between £35,858 and £41,377. The successful candidate will be placed on the scales according to skills and experience. For successful candidates based in West Africa, additional overseas benefits may be applicable.

For further particulars and an application form, please contact:

The Personnel Office, LSHTM,

Telephone 020 7927 2203 (24 hour answer phone) or e-mail personnel@lshtm.ac.uk quoting reference BG_IPTp. Only applications in the format outlined in the recruitment pack will be considered.

Closing date for applications is 23 May 2008.

Shortlisted candidates will be interviewed the week commencing 30th June 2008. For more information about the School, please visit www.lshtm.ac.uk.

The London School of Hygiene & Tropical Medicine is committed to being an equal opportunities employer.

Submission Deadline – May 28

Other Conference Application Deadlines:
Young Investigator Award – Due May 28
ASTMH Travel Award – Due May 28
ACME Travel Award – Due June 11
Elsevier Student Book Award – Due September 15

We look forward to seeing you at the ASTMH 57th Annual Meeting, to be held December 7-11, 2008 at the Sheraton New Orleans in New Orleans, Louisiana.

Call for Abstracts
Submission Deadline – May 28
Click here to view abstract submission information: http://www.astmh.org/meetings/education.cfm

Young Investigator Award
Application Deadline – May 28
This award recognizes developing young scientists who are pursuing careers in various aspects of tropical disease research.
Click here to download an application.

ASTMH Travel Awards
Application Deadline – May 28
Limited funding is available to support annual meeting travel of selected students and young investigators from developing countries and the United States. 
Click here to download an application.

American Committee of Medical Entomology (ACME) Travel Awards
Application Deadline – June 11
Limited funding is available to support annual meeting travel for graduate students who plan to submit an abstract(s) pertaining to arthropods of medical importance.
Visit to download an application.

Elsevier Student Book Award
Application Deadline – September 15
This award recognizes excellence in clinically-oriented research presented by a student or person in graduate medical training at the annual meeting.
Click here to download an application.

Pre-Meeting Courses
Clinical Pre-Meeting Course:
Malaria Eradication: Are We Ready to Try Again?
December 6-7, 2008
With the maturation of the debate on malaria eradication strategy, this course will focus on the progress and challenges of sustaining and expanding global support of malaria control.

Parasitology Pre-Meeting Course:
Whole Genome Association Studies: 
Understanding the Genetic Basis of Susceptibility to Infectious Diseases
December 6, 2008
This course will target scientists, physicians, clinicians, graduate students and educators with interests in the rapidly evolving field of whole genome association studies and how these approaches can be used to understand the basis for susceptibility or resistance to infectious diseases.  Topics will include an overview of whole genome association, a review of the state of the art in technology development, an overview of computational analyses and biostatistics and a discussion of some of the bioethical considerations associated with these studies.

Conference Updates
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Contact info@astmh.org with questions.  Thanks for your support of the ASTMH annual meeting.
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Noor AM, Moloney G, Borle M, Fegan GW, Shewchuk T, Snow RW.
The use of mosquito nets and the prevalence of Plasmodium falciparum infection in rural South Central Somalia. PLoS ONE. 2008 May 7;3(5):e2081.
There have been resurgent efforts in Africa to estimate the public health impact of malaria control interventions such as insecticide treated nets (ITNs) following substantial investments in scaling-up coverage in the last five years. Little is known, however, on the effectiveness of ITN in areas of Africa that support low transmission. This hinders the accurate estimation of impact of ITN use on disease burden and its cost-effectiveness in low transmission settings…

Doherty CP, Cox SE, Fulford AJ, Austin S, Hilmers DC, Abrams SA, Prentice AM.  Iron incorporation and post-malaria anaemia.  PLoS ONE. 2008 May 7;3(5):e2133.
Iron supplementation is employed to treat post-malarial anaemia in environments where iron deficiency is common. Malaria induces an intense inflammatory reaction that stalls reticulo-endothelial macrophagal iron recycling from haemolysed red blood cells and inhibits oral iron absorption, but the magnitude and duration of these effects are unclear...

Bate R, Coticelli P, Tren R, Attaran A.  Antimalarial drug quality in the most severely malarious parts of Africa - a six country study.  PLoS ONE. 2008 May 7;3(5):e2132.
A range of antimalarial drugs were procured from private pharmacies in urban and peri-urban areas in the major cities of six African countries, situated in the part of that continent and the world that is most highly endemic for malaria. Semi-quantitative thin-layer chromatography (TLC) and dissolution testing were used to measure active pharmaceutical ingredient content against internationally acceptable standards...

Wilson NO, Adjei AA, Anderson W, Baidoo S, Stiles JK. Detection of Plasmodium falciparum histidine-rich protein II in saliva of malaria patients. Am J Trop Med Hyg. 2008 May;78(5):733-5
Detection of Plasmodium falciparum parasites in patients with malaria necessitates drawing blood, which increases the risk of accidental infections and is poorly accepted in communities with blood taboos. Thus, non-invasive, cost-effective malaria tests that minimize the need for blood collection are needed. Plasmodium falciparum histidine-rich protein II (PfHRP II) levels in plasma and saliva were compared in malaria-positive and -negative patients in Ghana...

Enevold A, Lusingu JP, Mmbando B, Alifrangis M, Lemnge MM, Bygbjerg IC, Theander TG, Vestergaard LS. Reduced risk of uncomplicated malaria episodes in children with alpha+-thalassemia in northeastern Tanzania. Am J Trop Med Hyg. 2008 May;78(5):714-20
The prevalence of human red blood cell (RBC) polymorphisms is high in areas of intense Plasmodium falciparum transmission, and individuals carrying these genetic traits are believed to be partially protected against severe malaria. However, it remains uncertain how RBC polymorphisms affect the susceptibility to uncomplicated malaria …

Okech BA, Meleshkevitch EA, Miller MM, Popova LB, Harvey WR, Boudko DY. Synergy and specificity of two Na+-aromatic amino acid symporters in the model alimentary canal of mosquito larvae. J Exp Biol. 2008 May;211(Pt 10):1594-602.
The nutrient amino acid transporter (NAT) subfamily is the largest subdivision of the sodium neurotransmitter symporter family (SNF; also known as SLC6; HUGO). There are seven members of the NAT population in the African malaria mosquito Anopheles gambiae, two of which, AgNAT6 and AgNAT8, preferably transport indole- and phenyl-branched substrates, respectively...

Skinner-Adams TS, McCarthy JS, Gardiner DL, Andrews KT. HIV and malaria co-infection: interactions and consequences of chemotherapy.  Trends Parasitol. 2008 May 2 [Epub ahead of print]
The global epidemiology of HIV/AIDS and malaria overlap because a significant number of HIV-infected individuals live in regions with different levels of malaria transmission. Although the consequences of co-infection with HIV and malaria parasites are not fully understood, available evidence suggests that the infections act synergistically and together result in worse outcomes...

ZAMBIA and Russia yesterday signed a US$7 million grant for the malaria national support programme.

Health Minister, Brian Chituwo, said yesterday that the fund, to be administered through the World Bank, would help scale up malaria interventions in the country.

Dr Chituwo said the grant would greatly contribute to regional efforts in controlling the killer disease.

The minister was speaking during the signing ceremony in Lusaka.

He said part of the money would be invested in human resource development to equip health personnel with skills in the provision of quality healthcare.

Dr Chituwo said the focus of the Zambian Government was on boosting the malaria control measures and working towards the elimination of malaria in the region and the world over.

“I have no doubt that the Russian trust fund will not only assist the Zambian Government in scaling up interventions but will contribute towards our regional efforts to control malaria,” he said.

He said the national malaria control programme, which was established to deal with malaria issues, was committed to facilitating equal access to quality and cost-effective malaria control and prevention interventions.

Dr Chituwo said he was happy that many health facilities now had a regular supply of anti-malarial drugs and increased coverage of insecticide treated nets.

Russian Ambassador to Zambia, Anvar Azimov, said the Russian government was happy with the achievements Zambia had made in the fight against malaria.

Dr Azimov said Russia was committed to supporting health and education sectors, which greatly benefitted the Zambian people.

The envoy said next year, Russia would set aside about US$5 billion to go towards the education, health and energy support projects in developing countries such as Zambia.

He said the funds under the Russian Development Agency Aid had been introduced to improve the lives of people in developing countries.

Speaking at the same function, World Bank country manager, Kapil Kapoor, said the bank estimated the economic impact of malaria on the Zambian economy at approximately 1.5 per cent of the Gross Domestic Product every year.

He said the bank, which had been tasked to spearhead the malaria fund, was happy with the determination the Zambian Government had shown in dealing with malaria cases.

Canadian scientists working with Ugandans at Makerere University have reported that their novel drug candidates to treat malaria have demonstrated good safety in their first toxicity tests in animals.

This was announced on Monday in a press release by the Canada-based Upstream Biosciences Inc. The institute was founded in 2004 in the Canadian province of British Colombia.

“Researchers reported that Upstream’s anti-malarial candidates were well tolerated, with no signs of serious toxicity at likely healing dosages,” the release reads in part.

According to the researchers, activity in this range in a new class of anti-malarial drugs has the potential to represent an important advance in the treatment of a resistant form of the disease.

The release said the new data represents the third set of positive toxicity results in animals obtained by researchers at Makerere University for Upstream’s drug candidates for malaria, trypanosomiasis and leishmaniasis, all diseases caused by related parasites.

“These first positive toxicity results in animals for our anti-malarial candidates mark an important step in our programme to develop safe and effective drugs to fight this pervasive condition,” Mr Joel Bellenson, CEO Upstream was quoted as saying.

However, in a follow-up interview with Daily Monitor, Mr Bellenson said researchers can now move on to testing the drugs in sick animals, “and we know how high a dosage ceiling we can use for this testing.”

Asked how soon human trials would begin, he said it was hard to make precise predictions about the timing of trials.

He added: “Drug development has several stages and sometimes requires taking one step back to make two steps forward. When we get the animal efficacy data, it will tell us whether we need to use our artificial intelligence software to make the drugs more potent or less toxic.”

Mr Bellenson explained that the current malaria drugs have a similar mode of action and the parasites become resistant to chemicals related to these older drugs quite easily.

“Our compounds are a completely different chemical structure and are therefore likely to work by blocking different proteins activities,” he added.

“In addition, our compounds may have another advantage to work against sleeping sickness, Nagana and kala azar as well as malaria.

 This would simplify drug stocking logistics and administration to sick patients.” Malaria is the leading cause of illness and death in Uganda, accounting for 25-40 per cent of all outpatient visits at healthcare facilities.

Up to 20 per cent of all hospital admissions and 15 per cent of in-patient deaths are due to malaria.

Researchers from the Universities of Exeter and Coventry have developed the first new technique for diagnosing malaria able to challenge the rapid diagnostic tests (RDTs) currently used in the field. Early results, now published in the Biophysical Journal, suggest that the technique could be as effective as RDTs but far faster and cheaper, making it a potentially viable alternative. The team is now working on a non-invasive version of the device, which with the assistance of a team from the Royal Tropical Institute (KIT), Department of Biomedical Research in Amsterdam, it is planning to trial in Kenya later this year.

Two years in the making and funded by the European Union, this technique uses magneto-optic technology (MOT) to detect haemozoin, a waste product of the malarial parasite, in the blood. Haemozoin crystals are weakly magnetic and have a distinct rectangular form. They also exhibit optical dichroism, which means that they absorb light more strongly along their length than across their width. When aligned by a magnetic field they behave like a weak Polaroid© sheet such as used in sunglasses. This new technology takes advantage of these properties to give a precise reading of the presence of haemozoin in a small blood sample. The team has created a device, which gives a positive or negative reading for malaria in less than a minute.

The new device has a totally different approach from RDTs, which use a chemical agent to detect antigens associated with the malarial parasite. One of the problems with RDTs is that they need to be kept within a given temperature range, which is difficult in hot climates. These disposable kits cost between $1.50 and $4.50 each and take around 15 minutes to deliver a reading.

High-power microscopy is still the best method available for malaria diagnosis and has been used for more than a century. Unfortunately it is time-consuming and requires expensive equipment and specialist medical skills, which are rarely available in villages in rural areas in malaria endemic countries. Over the last decade RDTs have been developed, which allow for faster diagnosis in the field, but these are too costly to be viable for developing countries. Furthermore, RDTs are often not stable at relatively high temperatures and sometimes remain positive even after successful treatment. In many communities where malaria is having a severe impact on health, there is no testing for malaria and young children who have a fever are given anti-malaria drugs as a matter of course. This has contributed to the malarial parasite becoming increasingly resistant to the common anti-malaria drugs. Malaria is a disease for which there is still no vaccine.

Professor Dave Newman of the University of Exeter’s School of Engineering, Computing and Mathematics, said: "There is an urgent need for a new diagnostic technique for malaria, particularly in the light of global warming, which threatens to spread the disease into new parts of the world, including southern Europe. The early results from our device are very promising and hugely exciting. We expect to ultimately produce a sensitive non-invasive device that will be cost effective and easy to use, making it suitable for developing countries, where the need is greatest."

This research was carried out by the University of Exeter, University of Coventry and KIT Biomedical Research, Amsterdam and was funded under the European Commission Framework 6 Program.

A generation after the first attempt failed, people are once more talking seriously about eradicating malaria.

The fight against the ancient, mosquito-borne disease has newfound support almost everywhere, including in the National Basketball Association. The world’s richest charity, the Bill and Melinda Gates Foundation, is leading the charge. There’s an effective drug -- artemisinin -- that wasn’t around 30 years ago, and a consumer product -- insecticide-treated bed nets -- that together are saving tens of thousands of lives.

But whether that will lead one day to the last case of malaria is an open question -- and one that will take another generation to answer.

Yesterday, on the first World Malaria Day, the prospect hovered somewhere between useful fantasy and distant hope.

"Why can’t we set our dream high?" Margaret Chan, the World Health Organization’s director-general, asked soon after arriving in Washington for events here and in New York. "I don’t think we can deny the countries of Africa that possibility, even though we realistically know it will take a long time."

About 500 million people get malaria each year and about 1 million die, the vast majority African children younger than 5. Worldwide, about 2.37 billion people in 87 countries are at risk of the disease, which is caused by a parasite called plasmodium that is passed from person to person by mosquitoes.

The first call for eradication came in 1955 from the World Health Assembly, which consists of the health ministers of U.N. member countries. It was confident that DDT, an insecticide whose use during World War II had dramatically reduced malaria, coupled with postwar economic development could stop the disease.

(Only one eradication effort has succeeded. Smallpox was officially declared gone in 1980 after a campaign that began in 1966.)

The malaria effort lasted 14 years, cost about $1.4 billion and in some places eclipsed other efforts to improve health. By the time the World Health Assembly lowered its goal to malaria "control," 18 countries had become malaria-free, including Spain, Cuba, Taiwan and most of Eastern Europe.

But no countries in Africa, where transmission often occurs year-round, got rid of the disease. Some came close only to see malaria roar back. Sri Lanka recorded only 18 cases in its best year; it now has about 10,000 a year.

The failure greatly disheartened the public-health community. Malaria rejoined malnutrition, diarrhea and pneumonia as seemingly inevitable threats to poor people in the developing world.

This fatalism at least partly set the scene for a resurgence of the disease in recent decades. However, money is pouring again into malaria control -- about $1 billion a year, 10 times the amount of a decade ago.

The big funders include the Global Fund to Fight AIDS, Tuberculosis and Malaria, which since 2002 has given $2.5 billion to fight the disease, and President Bush’s Malaria Initiative, launched in 2005 with a goal of spending $1.2 billion over five years.

Much of the money is going for drugs and mosquito nets permanently impregnated with insecticide. Widespread use of nets has helped Rwanda and Ethiopia reduce child malaria deaths by more than 50 percent in the past three years. A charity called Nothing but Nets has raised enough money to buy nearly 2 million $10 nets, with help from the NBA and many schoolchildren.

Bush marked the occasion yesterday at a Boys & Girls Club in Hartford, Conn. About 150 clubs around the country raised $25,000 for nets.

"I know the boys and girls will probably never meet any of the lives who are being saved. I had the honor of traveling to Africa, and I can assure all who’ve been helping, the people of Africa are most grateful to the American citizens for their help," he said.

The strategy of spraying indoor walls of houses with insecticides, including DDT, once or twice a year is also making a comeback.

The cost of scaling up prevention, treatment and surveillance to fully cover malaria-afflicted areas is $3.8 billion to $7 billion a year, according to two recent estimates.

That huge amount did not deter Bill and Melinda Gates. At a malaria summit they held in Seattle last October, the Gateses called for the eradication of malaria. WHO’s Chan did not know the announcement was coming but gave it what many took as an unofficial endorsement when she told the audience, "I dare you to come along with us."

Most malaria experts, however, say the goal is currently unfeasible.

That’s because transmission rates in "hyper-endemic" parts of Africa are 100 times higher than in any place where the disease has been eliminated. There is no vaccine; without one, eradication is hard to imagine. One candidate tested in Africa reduced infections by 35 percent over two years; a much more effective one is not expected for more than a decade.

In a paper prepared for the British government in December, three malaria experts wrote that "it is not unthinkable that global eradication can be achieved, but it is not possible with current methods."

That doesn’t bother Richard Feachem, former head of the Global Fund and now at the University of California at San Francisco.

He and others espouse a two-pronged strategy -- aggressive control in the high-transmission parts of Africa, while simultaneously "shrinking the malaria map" by eliminating the disease from places where it is less intense. The latter includes islands in Oceania, parts of southern Africa and China. He believes that by the time eradication becomes a possibility in Africa, there will be new tools.

"The overall effort is measured in decades," he said recently.

Dates: 23 - 27 June 2008

Location: Dar es Salaam, Tanzania

Deadline for Applications: 30 May 2008

http://www.amanet-trust.org/ext/news/AHRECall2008.html

Background/Rationale

The high disease burden of African countries, the emergence of new diseases, and efforts to address the10/90 gap, have led to an unprecedented increase in health research activities in Africa. In light of the generally poor health delivery systems, the lower levels of education, and poverty of communities and governments, it has become imperative that HRE in Africa be strengthened in order to minimise the risk of unethical research being conducted on the poor populations.

Historically, research participants and research institutions have been exposed to abuse and are inadequately prepared to handle complexities that characterize justice and beneficence desirable for research involving human participants and communities.  This is ever so important in the less developed world where regulatory systems are either very weak or non existent in majority of cases.

Over the next three years, and through a grant from The Bill and Melinda Gates Foundation, AMANET will organize a series of 5 workshops on Advanced Health Research Ethics (HRE) primarily for health investigators and secondarily for Ethics Committee members and policy makers. Since the workshops will be at an advanced level, basic HRE training will be a pre-requisite. The first workshop will be held in Dar es Salaam from 23 to 27 June 2008.

Precedence:

AMANET continues to champion the need for training in biomedical research ethics to various stakeholders of research in Africa. With regard to health research ethics for ethics review committees, the following workshops have been organized by AMANET:

1. Workshops on Ethics in Health Research in Africa,  in Kenya (Kisumu, 2001), Ethiopia (Addis Ababa,   2001), South Africa (2002, Pretoria), Gabon, (Libreville, 2002), Sudan (Khartoum, 2003), Cameroon (Yaoundé, 2003), Ethiopia (2007), Ghana (2008) Senegal (in French, 2008) and Tanzania (Dar es Salaam, 2005, 2006 and 2007)
2. Workshop on Standard Operating Procedures for Ethics Review of Health Research in Africa, 17-21 February 2003, Entebbe, Uganda;
3. Workshop on Advanced Ethics in Biomedical Research that Involves Human Subjects, 1-3 December 2004, Zanzibar, Tanzania; and
4. Workshop on Protection of Human Research Participants: Writing of Standard Operating Procedures for Ethics Review Committees in Eastern Africa: 29-31 August 2005, Dar es salaam, Tanzania.

Reports on the above activities are available in the various issues of the AMANET Newsletter available online at: www.amanet-trust.org.   

Workshop Pedagogical Methods

The workshop will apply participatory approaches including overviews, case studies, discussion groups, panellists, and participants presentations and other interactive and adult teaching/learning methods. To broaden discussions special panels for some of the topics will be convened. Lecture type presentations will be followed by question and answer sessions. Experienced facilitators have been carefully selected from within Africa.  

Workshop Participants (Selection)

Basic HRE training and participation in the AMANET online HRE Discussion Forum will be considered in the selection process. The online Discussion Forum can be accessed via the AMANET website; some of the case studies discussed online will be used during the workshop. The target candidates are health researchers, but few places may be available for applicants outside these criteria. Interested candidates who meet the selection criteria should submit their applications by the 30th of May 2008.

Workshop Objectives

This workshop aims firstly to flag topical ethical issues that are relevant to health research in developing country settings, and secondly to explore various schools of thought with the aim of coming up with well thought out positions and/or recommendations. Examples and case studies pertinent to Africa will be used. The following are the highlights of the topics to be covered:

1. Applying Ethical principles in Health Research and Ethical review process
2. Responsibilities in Health Research
3. Ethical issues in research design and recruitment of research participants.
4. Research with vulnerable persons and groups
5. Legal and social issues in Health Research Ethics
6. Ethical Issues in international collaborative health research 
7. Models and practicalities of community consultation
8. Ethical issues surrounding the 10/90 gap
9. Ethical issues in traditional medical practice and “research”
10. Professional Ethics
11. Animal Research Ethics

Workshop Outcomes

By the end of the five day workshop, it is further hoped that:

1. Participants will be brought up to date with topical ethical issues around current research   practices;
2. Participants will be able to address ethical issues at the design stage of health research and be able to enhance the protection of the welfare of research participants when implementing health research protocols.  

Language:

The workshop will be conducted in English; there will be no translations to other languages.

Workshop Reports:

Three participants will be nominated to be rapporteurs for the workshop. Proceedings will be recorded for publication in the AMANET newsletter and will be available for participants. 

AMANET Scholarship:

Selected participants will be awarded scholarships by AMANET, which will cover costs for economy class airfares (where needed), visas, tuition and accommodation and meals. Participants should meet all their home country transit costs.

Timelines:

1. This call sent out on or before 30 April 2008
2. Applications should reach AMANET secretariat no later than 30 May 2008
3. Please note that only short-listed candidates will be contacted, a list of selected candidates will be made available on the AMANET web site.
4. Selected participants will be informed by 15 June 2008

Applications (with brief CVs and one-half page justification) should be submitted by email to: 

The Managing Trustee,
African Malaria Network Trust,
Tanzania Commission for Science and Technology Building,
PO Box 33207,
Dar es Salaam, Tanzania.
E-mail: info@amanet-trust.org
Fax: +255 22 2700380
www.amanet-trust.org

Acknowledgements

The workshop is supported by a grant to AMANET from the Bill and Melinda Gates Foundation on strengthening institutional health research ethics in Africa.

Location: Abuja, Nigeria

Deadline for Applications: 12 May 2008

Background

Malaria Consortium is a leading international organisation working in Africa and Asia as well as at global level on communicable disease control. Malaria Consortium manages a large number of communicable disease projects in a number of countries. These projects range from technical support at central government level to direct implementation of projects for the control of malaria, tuberculosis, diarrhoeal diseases and neglected tropical diseases at district and community levels.

Malaria Consortium recently won a large-scale, £50 million DFID-funded five year, comprehensive malaria control programme in Nigeria. Malaria Consortium is seeking a dynamic individual with extensive experience of malaria control to be the lead technical person in this exciting, innovative and influential new public-private partnership programme in Nigeria.

Key roles and responsibilities

1. Be responsible for all technical inputs on malaria, particularly treatment, to the project
2. Work with Malaria Consortium technical team to refine project strategies, develop plans, and coordinate technical monitoring, evaluation and operational research
3. Technically support FMoH in the development of malaria policies, strategies, implementation plans and training materials, particularly on treatment
4. Ensure project, NMCP and states link malaria control activities within a health systems strengthening approach
5. Design and oversee the implementation of malaria case management training programmes for the public and private sectors, including for patent medicine vendors
6. Put in place quality assurance procedures and monitoring systems for case management strengthening
7. Provide technical inputs to the commercial sector pharmaceutical partnership on malaria treatment issues
8. Support NMCP and states implement and monitor intermittent preventive therapy for pregnant women
9. Oversee routine and campaign distributions of long-lasting insecticide treated nets
10. Represent Malaria Consortium and the project on malaria technical working groups

Line manager: Programme Director

Location: Abuja, Nigeria and frequent in-country travel and occasional international travel

Skills and experience:

1. Medical degree and postgraduate qualification in international health or related discipline
2. Minimum of ten years experience in malaria control in Africa, including some at international level
3. Proven technical skills in malaria, including malaria case management
4. Experience and understanding of working with Ministries of Health in policy and strategy formulation
5. Experience of training health workers, preferably both public and private sector (formal and informal)
6. Experience and understanding of Nigerian context (desirable)
7. Significant experience in project management
8. Excellent writing and presentation skills

A competitive package and long term contract will be provided to the successful candidate.

For more details please see www.malariaconsortium.org 

A CV with a 2 side covering letter should be submitted by email to Ian Gavin at i.gavin@malariaconsortium.org  by Monday 12th May 2008.

Samarasekera U.  Drug subsidy could help Tanzania tackle malaria.  Lancet. 2008 Apr 26;371(9622):1403-6
No Abstract...

Shetty P.  Fred Binka: fighting malaria in Africa.  Lancet. 2008 Apr 26;371(9622):1409
No Abstract...

Chambers RG, Gupta RK, Ghebreyesus TA.  Responding to the challenge to end malaria deaths in Africa.  Lancet. 2008 Apr 26;371(9622):1399-401
No Abstract...

Todryk SM, Bejon P, Mwangi T, Plebanski M, Urban B, Marsh K, Hill AV, Flanagan KL. Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 T cells with susceptibility in Kenyans. PLoS ONE. 2008 Apr 30;3(4):e2027
Immunity to malaria develops naturally in endemic regions, but the protective immune mechanisms are poorly understood. Many vaccination strategies aim to induce T cells against diverse pre-erythrocytic antigens, but correlates of protection in the field have been limited. The objective of this study was to investigate cell-mediated immune correlates of protection in natural malaria...

Santolamazza F, Calzetta M, Etang J, Barrese E, Dia I, Caccone A, Donnelly MJ, Petrarca V, Simard F, Pinto J, Della Torre A. Distribution of knock-down resistance mutations in Anopheles gambiae molecular forms in west and west-central Africa. Malar J. 2008 Apr 29;7(1):74 [Epub ahead of print]
Knock-down resistance (kdr) to DDT and pyrethroids in the major Afrotropical vector species, Anopheles gambiae sensu stricto, is associated with two alternative point mutations at amino acid position 1014 of the voltage-gated sodium channel gene, resulting in either a leucine-phenylalanine (L1014F), or a leucine-serine (L1014S) substitution…

Mueller DH, Wiseman V, Bakusa D, Morgah K, Dare A, Tchamdja P. Cost-effectiveness analysis of insecticide-treated net distribution as part of the Togo Integrated Child Health Campaign. Malar J. 2008 Apr 29;7(1):73 [Epub ahead of print]
...To evaluate the cost-effectiveness of the first nationwide delivery of long-lasting insecticide-treated nets (LLITNs) as part of the 2004 measles vaccination campaign in Togo to all children between nine months and five years...

Cohen ER, O’Neill JM, Joffres M, Upshur RE, Mills E. Reporting of informed consent, standard of care and post-trial obligations in global randomized intervention trials: A systematic survey of registered trials.  Dev World Bioeth. 2008 Apr 28 [Epub ahead of print]
Ethical guidelines are designed to ensure benefits, protection and respect of participants in clinical research. Clinical trials must now be registered on open-access databases and provide details on ethical considerations. This systematic survey aimed to determine the extent to which recently registered clinical trials report the use of standard of care and post-trial obligations in trial registries, and whether trial characteristics vary according to setting...

Tyagi RK, Sharma PK, Vyas SP, Mehta A. Various carrier system(s)- mediated genetic vaccination strategies against malaria. Expert Rev Vaccines. 2008 May;7(4):499-520
The introduction of vaccine technology has facilitated an unprecedented multiantigen approach to develop an effective vaccine against complex pathogens, such as Plasmodium spp., that cause severe malaria. The capacity of multisubunit DNA vaccines encoding different stage Plasmodium antigens to induce CD8(+) cytotoxic T lymphocytes and IFN-gamma responses in mice, monkeys and humans has been observed. Moreover, genetic vaccination may be multi-immune (i.e., capable of eliciting more than one type of immune response, including cell-mediated and humoral). In the case of malaria parasites, a cytotoxic T-lymphocyte response is categorically needed against the intracellular hepatocyte stage while a humoral response...

Malaria continues to haunt 40% of the world’s population. It infects more than 500 million people per year and kills more than 1 million. The burden of malaria is heaviest in sub-Saharan Africa but the disease also afflicts Asia, Latin America, the Middle East and even parts of Europe.

World Malaria Day - which was instituted by the World Health Assembly at its 60th session in May 2007 - is a day for recognizing the global effort to provide effective control of malaria. It is an opportunity:

• for countries in the affected regions to learn from each other’s experiences and support each other’s efforts;
• for new donors to join a global partnership against malaria;
• for research and academic institutions to flag their scientific advances to both experts and general public; and
• for international partners, companies and foundations to showcase their efforts and reflect on how to scale up what has worked.

On this year’s World Malaria Day, the Roll Back Malaria Partnership - which includes WHO - will focus on malaria as a global health problem. The partners will engage the international community in their fight against malaria.

Today, 25 April 2008, the first World Malaria Day is being commemorated globally under the theme: “Malaria – a disease without borders”. Concurrently, the African Region is celebrating Africa Malaria Day, under the slogan: ‘‘United to Combat Malaria” This slogan underscores the urgent need to scale up malaria control interventions.

In countries where malaria is highly endemic, priority should be given to accelerating implementation of cost-effective interventions and strengthening surveillance, monitoring and evaluation systems to enable us to measure progress. The benefits of scaling up interventions are already being reaped in countries such as Eritrea, Ethiopia, the Gambia, Sao Tome & Principe, South Africa, Swaziland, Tanzania and Togo. In Rwanda, strong commitment and investment, since 2005, has led to the distribution of 3 million Long-Lasting Insecticide-treated Nets (LLINs) and constant supply of medicines for Artemisinin-based combination therapy in health facilities. As a result, in 2007, outpatient malaria cases among all age groups fell by 36%, malaria admissions decreased by 55% while malaria deaths dropped by 35% .Cross-border initiatives such as The Lubombo Spatial Development Initiative between the governments of Mozambique, South Africa and Swaziland have helped reduce malaria transmission in target areas. These successes show that coordinated support, increased financing and intercountry initiatives are critical for making a good impact. We must systematically document and share these best practices.

We must recognize that the vision of eliminating malaria will only become reality through countrywide implementation of interventions. That will require improved governance and accountability, increased advocacy, better communication, social education and mobilization, and predictable and sustainable financing from governments and development partners In this regard, coordination of the efforts of all stakeholders in the public and private sectors and in civil society is crucial. There is need to strengthen health systems and community-based interventions Improved partnerships are needed to sustain and consolidate achievements.

Accelerating progress in the continuum from malaria control to malaria elimination will require increased resources for thorough analysis and appropriate response to implementation bottlenecks and for rigorous monitoring and evaluation of performance

That is why we must be ‘‘United to Combat Malaria”.

Let us unite our efforts to ensure:

• that all those at risk of malaria including children, pregnant women, people living with HIV and AIDS, refugees and displaced people, victims of environmental disaster and civil strife in our Region have access to Long-Lasting Insecticide-treated Nets;
• that, where appropriate, Indoor  Residual Spraying (IRS) with effective insecticides is applied;
• that malaria can be promptly and correctly diagnosed;
• that patients receive timely treatment using life-saving Artemisinin-based Combination Therapies (ACTs).
• that every pregnant woman has access to prevention and treatment to protect herself and her unborn child from malaria.

We encourage all Member States, partners and stakeholders in malaria control to build upon our common achievements and adjust to the changing malaria landscape in order to accelerate the improvement of health in the African Region.

Let us all be ‘‘United to Combat Malaria”

Thank you.

It looks a bit like the coolers used to keep drinks fresh on a sunny day but the chill box being tested in sweltering Mozambique serves a higher purpose - saving lives from malaria.

The new cool box is intended to keep malaria medicines at 25 degrees Celsius or below in impoverished rural areas without electricity where temperatures can reach 45 degrees Celsius.

As the world marks Malaria Day on Friday, its developers hope the cool box will help save some of the one million lives lost to malaria worldwide every year - 6 000 of them in Mozambique alone.

"At the beginning, the cool boxes will be used to store malarial drugs such as the rapid diagnostics tests for malaria," said Parfait Komlan Edah, advisor to John Snow Incorporated, a US company developing the coolers.

"We will change the treatment pattern and procedure because the drugs are expensive and they have to be well preserved to be effective," he said.

The project, funded by the US Agency for International Development, started in 2006 and is still at an experimental phase. The coolers are currently being tested in three regions of Mozambique - Maputo, Tete and Zambezia.

The tests will determine whether the coolers are adopted for use nationwide.

A report last year by the UN Children’s Fund (Unicef) and the Roll Back Malaria Partnership found that supplies of new medicines and insecticide-treated bednets were helping prevent child malaria.

But in Mozambique, malaria is still the leading cause of death among children admitted to paediatric services and there has been an increase in cases of malaria in recent years.

Faced with the upsurge in malaria, Mozambique’s health ministry in 2007 decided to expand the use of rapid diagnostics tests for the disease that can give a result within minutes.

The only trouble was that diagnostics tests have to be stored at temperatures of 25 degrees Celsius or below and are currently only available in provincial hospitals that have refrigeration facilities.

"The project was faced with the dilemma of how to ensure quality products despite the hot, humid weather and lack of electricity common in remote health facilities," Edah said.

The solution was to devise "evaporative coolers" - similar in size to a small refrigerator and made of aluminium, steel and burlap.

The coolers have a water tank at the top that is regularly refilled. When water evaporates from the tank it passes along wicks that stick out of the cooler, keeping the contents of the box cool.

The cooler project receives some of its funding from US President George Bush’s President’s Malaria Initiative, which also sponsors other initiatives such as mosquito nets and awareness programmes.

The initiative spent $18-million (about R137-million) in Mozambique in 2007.

In a message on World Malaria Day, which is being commemorated under the theme "Malaria - a disease without borders," the World Health Organisation (WHO) stressed the importance of national malaria programmes.

"We must recognise that the vision of eliminating malaria will only become reality through countrywide implementation of interventions," including through national health systems and community projects, the WHO said in a statement.

Nelson Nkini, head of Proserv, a Mozambican non-governmental group supplying mosquito nets treated with anti-malarial substances, said preventing the disease was cheaper than curing it because of the cost of medicines.

"Our appeal is to everybody living in rural areas, where effective medication is not available, to use treated mosquito nets to prevent the spread of the disease," Nkini said. "Prevention is cheaper than cure."

British entrepreneur, 25, created world’s top soccer website; now teams with leading global health professors to innovate in malaria philanthropy

Public offered chance of involvement in African malaria research projects

Philanthropy just got easier and a lot more accessible to the public thanks to the social networking power of the Internet and a ground-breaking partnership between a young British entrepreneur, a global health think tank and an African medical research institute.

Debuted April 20 to offer individuals a meaningful way to mark World Malaria Day (Friday, April 25), its creators hope www.MalariaEngage.org will do for African research what YouTube did for sharing videos and what eBay did for trading things – open it up in a creative and engaging way to the vast global community through the World Wide Web.

At MalariaEngage.org, people can enlist directly in the anti-malaria battle by contributing $10 or more to an initial choice of seven highly varied projects involving selected scientists in developing countries.  Over time, new projects will replace those that reach their funding goal (the original seven have objectives ranging from $10,000 to $50,000). The site features a discussion area where supporters can interact with researchers and each other, obtain news and photos of both funded and proposed projects, a running tally of money raised, and stories from the front lines in the war against the scourge of malaria. 

Borne by mosquitos, malaria is a preventable disease that infects an estimated 515 million people yearly and kills between one and three million annually, the vast majority of them children in sub-Saharan Africa -- an estimated 3,000 child victims daily.

It is the leading cause of death in Tanzania, where the National Institute for Medical Research (NIMR) researchers proposed the initial suite of seven cutting-edge projects chosen to launch MalariaEngage.org.

The team behind MalariaEngage.org includes 25-year-old Tom Hadfield, a self-described "part-time student and full-time entrepreneur" who came to national attention in his native Britain when Soccernet, a website he developed as a high school student in his bedroom, was sold at age 17 to ESPN for $40 million.

Honoured as a Global Leader of Tomorrow by the World Economic Forum in Davos, Switzerland, in 2001 and now studying at Harvard, Tom has parlayed his dot-com success and passion for launching entrepreneurial projects into innovative ways of tackling the planet’s oldest and most intractable problems.

"It’s shocking that thousands of people are dying every day from a preventable disease," says Hadfield.  "When I came back from Africa last summer, a lot of people asked me what they can do to help. 

"By encouraging individual participation and involvement, we will create international communities of common interest," he says. "This is the essence of social networking – MalariaEngage.org connects people who want to help directly with researchers working in Africa on malaria prevention, treatment and capacity building projects. Everyone can help and I urge them to discover, learn, join, contribute, get results, share experiences and invite others to participate."

Hadfield notes MalariaEngage.org will fit seamlessly into other social networking sites such as Facebook, whose users can add malaria research projects as a "cause" on their profile, join groups of project supporters, and communicate with others dedicated to helping eradicate malaria.

"When we tap into all that energy and creativity to promote and raise funds for malaria research projects, not just in Tanzania but elsewhere in Africa and the developing world, who knows what might be achieved?"

Hadfield co-founded MalariaEngage.org with leading global health professors Peter A. Singer and Abdallah S. Daar at Canada’s McLaughlin-Rotman Centre for Global Health at University Health Network and University of Toronto (MRC), the project’s lead partner.

Says Dr. Singer, MD: "Everyone recognizes that one of the most significant ethical challenges facing the world today is the inequity in global health.  Life expectancy in industrialized countries is 80 years and rising; whilst in many Afrcian countries it is 40 years and falling.  The key ethical value underlying efforts to do something about these inequities is solidarity.

"Many young people in the US, Canada, Europe and other industrialized countries feel a sense of solidarity with kids in Africa, but there is not much they can do to act on this ethical intuition.  MalariaEngage.org was designed to give them a channel to do something in practice about that ethical value of solidarity, to mobilize a vast untapped pool of support – not just to raise funds but also to create a worldwide community of people committed to changing the face of global health," he says.

"Imagine a world where like-minded people in the US, Canada, Europe and other industrialized nations are tightly connected in efforts to find solutions to malaria – one of the great, and unnecessary, plagues affecting humankind."

According to Dr. Daar, MD:  "Malaria is an ongoing global health catastrophe that must be addressed by empowering researchers in the developing world to find solutions to their countries’ own problems through creative, properly capitalized research programs.  Tapping the talent and motivation of developing country scientists is critical if we’re going to win this fight."

If this initial proof of concept is successful, MalariaEngage.org will scale up by involving other African-based institutions fighting malaria, he adds.

Detailed descriptions of the seven malaria research projects follow.

* * * * *

Plants that repel mosquitoes

The mosquito-repellant properties of certain plants and shrubs have been known for years but it wasn’t until a few years ago that the idea of targeted plantings to fight malaria was put to the test at the Lukole refugee camp in Tanzania’s Ngara district.  When lantana, lemongrass, Mexican marigold, American basil and other seedlings were grown around camp houses, mosquito bites and malaria cases in the camp dropped significantly.

Hamisi Malebo, a NIMR researcher specializing in natural products, traditional medicine and traditional anti-mosquito agents and health systems, is principal investigator on a project to establish large-scale production of the seeds and seedlings of eight plants and shrubs known to repel or kill mosquitoes. The aim is to distribute seedlings and instructions on where and how to plant them to every malaria-prone region of Tanzania.

The main plant nursery will be established at Amani Medical Research Centre in north-east Tanzania, an area where malaria causes many deaths, especially among young children and pregnant women. Smaller nurseries will be established in 10 nearby villages with high infection rates. The other goal of Malebo’s project is to extract the plants’ oils to make mosquito repelling creams and lotions, as well as mosquito coils that burn for several hours.

Insecticide treated mosquito nets

Research in malaria-prone regions of sub-Saharan Africa shows that insecticide-treated mosquito nets (ITNs) can reduce infections by 50% and malaria-related child deaths by 20%. Despite the efforts of international aid agencies and NGOs, which have distributed millions of free ITNs throughout Africa, the lifesaving nets are not readily available in many of the rural areas where 80% of people at risk of getting malaria live.

NIMR research scientist Emanuel Makundi is leading a project looking for solutions to the problems of access – including the high cost of ITNs ($6.50 each, putting them out of reach of many households) – as well as the social and cultural factors preventing more widespread use of the nets in malaria areas.

Muslims, for example, do not use white bed sheets as religious burial cloths are white. They will not use the white mosquito nets for the same reason. In coastal communities, some fishermen prefer to use the mosquito nets to catch fish.

The NIMR project is focusing on education, with particular emphasis on school children and youth groups as well as community leaders, local organizations, religious groups and traditional healers. Community owned resource persons (CORPs) are being recruited to lead the education initiative which will be reinforced with community-based payment and distribution programs.

Drug combination therapy

Combination therapy to treat malaria is the simultaneous use of two or more drugs that kill the plasmodium parasite in different ways. NIMR researcher Dr. pJulius Massaga is investigating the combination of Artesunate, one of the artemisinin family of highly effective anti-malarial drugs, and artemether-lumefantrine, Tanzania’s drug of choice for treatment of uncomplicated malaria.

The study is focusing on children under five. They are typically the most severe cases of malaria because they have developed no immunity through previous exposure. They need to be treated within 24 hours of the first symptoms to minimize the chances of simple malaria progressing to the severe complicated form of the disease which can be fatal.

Dr. Massaga is evaluating two different approaches to community-based treatment of infected children with Artesunate combination drug therapy: 

· Mother coordinators (MCs) – the village is divided into segments and each segment has a "mother" trained to oversee malarial fever management in small children.
· Community owned resource persons (CORPs) – One person in each village is trained to support malaria case management and act as a service delivery point.

At the first sign that a child has contracted malaria, he is taken to the MC or CORP, who administers the first dose of combination drugs. The remainder of the three-day, six-dose regimen is administered at home.

If  Dr. Massaga’s study determines that this Home Management of Malaria (HMM) strategy is feasible, socially acceptable, safe and effective, it could lead health policy planners to focus on scaling up HMM programs throughout Tanzania.  

Assessment of artemisinin drugs

Artemisinin is a strong antimalarial drug isolated from the Chinese anti-malarial traditional medicinal plant, Artemisia annua, commonly known as sweet wormwood. Artemisinin and its derivatives are the most powerful and efficient drugs ever discovered for the treatment of malaria.

Since 2000, artemisin-based combination therapies (ACTs) have become the first-line malaria treatment in the many African countries where drug-resistant strains of the disease have dramatically reduced the effectiveness of chloroquine and sulfadoxine / pyrimethane.

Tanzania is one of the countries where ACT (artemisinin in combination with artemether-lumefantrine) has had excellent results.  But many factors keep this treatment from reaching residents of the poor rural communities who need it most, including lack of health services in remote areas, distribution problems and cost.

Scientist Emanuel Makundi of NIMR will examine a range of issues related to ACTs – accessibility, affordability and drug use compliance – to discover the extent to which the new treatment has penetrated public and private health facilities at the community level and how access can be improved for poor people in rural areas.

Intermittent Preventive Treatment for pregnant women

Pregnant women and their unborn children are particularly vulnerable to the ravages of malaria. Maternal infection during the second half of pregnancy causes impaired foetal weight gain. Malaria infection of the placenta and malaria-caused maternal anaemia can lead to low birth weight, which contributes to higher infant mortality and impaired development.

Malaria causes an estimated 8-14% of all low birth weight babies and 3-8% of all infant deaths in malaria areas of Africa.  For the mothers, malaria is responsible for up to  15% of the 10,000 deaths from maternal anaemia in Africa each year.

Intermittent preventive treatment (IPT) – giving pregnant women preventive treatment doses of an effective antimalarial drug in the second and third trimesters – has been shown to be a safe, inexpensive and effective way to save the lives of mothers and their babies by reducing placental infections, maternal anaemia and low birth weight.

NIMR research scientist Dr. Julius Massaga is leading a wide-ranging education campaign to increase IPT coverage throughout rural Tanzania. While health workers are trained in the proper implementation of IPT, patients are targeted through media campaigns and community health education sessions explaining the benefits of the IPT strategy.

Sweet wormwood as a herbal remedy.

For many centuries, Chinese herbalists used the sweet wormwood plant (Artemisia annua) as a kind of all-round wonder drug. A tea made from its leaves was used to treat malaria as well as fevers, colds, diarrhea and bleeding. A poultice of leaves was placed on boils, abscesses and nose bleeds.

Western researchers began to focus on the plant’s specific anti-malarial properties in the early 1970s when they isolated and tested the active ingredient artemisinin. Subsequent trials have shown it to be a very effective malaria drug, even against multi-drug resistant strains of the disease.

But while access to the expensive artemisinin group of drugs is still problematical, especially for people living in the remote rural areas of Tanzania where malaria strikes most frequently, the sweet wormwood plant will grow virtually anywhere and is common throughout Africa.

NIMR scientist Vitus Nyigo leading a project to validate the safety and effectiveness of sweet wormwood as a cheaper, standardized malaria herbal remedy for use in remote rural areas. He is conducting clinical trials with malaria patients and investigating a concoction of sweet wormwood and two other plants he believes may help to synergize the parasite-killing properties of artemisis annua.

Improving collaboration between traditional healers and health workers

The relationship between traditional healers and health workers is often an uneasy one. The traditional healer may fear a loss of prestige and patients when health workers come to his village. Medical personnel, for their part, are often reluctant to cooperate with healers out of a genuine, but sometimes misplaced concern that their methods may harm the patient.

In the case of young children infected with malaria, traditional healers were often blamed for delaying medical treatment while they tried to drive out the evil spirits they believed were causing degedege or malarial convulsions.

That began to change in Tanzania thanks to a project to convince traditional healers and community members that when a child has the symptoms of severe malaria – convulsions and coma – the anti-degedege ritual must be postponed until after the patient receives urgent medical attention.

By actively involving traditional healers as treatment partners and encouraging them to refer young malaria victims to health facilities for immediate attention, the project lowered malaria mortality rates in the study area.

Building on that success, NIMR research scientist Emanuel Makundi’s project will look for ways to further improve communication and collaboration between traditional healers and health workers in addressing child malaria in remote rural communities.

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For more information: Terry Collins +1-416-538-8712 or +1-416-878-8712, terrycollins@rogers.com

Sakuntabhai A, Ndiaye R, Casadémont I, Peerapittayamonkol C, Rogier C, Tortevoye P, Tall A, Paul R, Turbpaiboon C, Phimpraphi W, Trape JF, Spiegel A, Heath S, Mercereau-Puijalon O, Dieye A, Julier C.   Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal. PLoS ONE. 2008 Apr 23;3(4):e2000
Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection...

Mok BW, Ribacke U, Rasti N, Kironde F, Chen Q, Nilsson P, Wahlgren M. Default Pathway of var2csa switching and translational repression in Plasmodium falciparum. PLoS ONE. 2008 Apr 23;3(4):e1982
Antigenic variation is a subtle process of fundamental importance to the survival of a microbial pathogen. In Plasmodium falciparum malaria, PfEMP1 is the major variable antigen and adhesin expressed at the surface of the infected erythrocyte, which is encoded for by members of a family of 60 var-genes. Peri-nuclear repositioning and epigenetic mechanisms control their mono-allelic expression. The switching of PfEMP1 depends in part on variable transition rates and short-lived immune responses to shared minor epitopes. Here we show var-genes to switch to a common gene that is highly transcribed, but sparsely translated into PfEMP1 and not expressed at the erythrocyte surface. Highly clonal and adhesive P. falciparum, which expressed distinct var-genes and the corresponding PfEMP1s at onset, were propagated without enrichment or panning...

Huh HJ, Oh GY, Huh JW, Chae SL. Malaria detection with the Sysmex XE-2100 hematology analyzer using pseudoeosinophilia and abnormal WBC scattergram. Ann Hematol. 2008 Apr 22 [Epub ahead of print]
Recent investigation using the Sysmex XE-2100 hematology analyzer (Sysmex Corporation, Japan) has demonstrated erroneously high eosinophil counts and abnormal white blood cell (WBC) scattergrams in malaria cases. This study was conducted to assess the diagnostic efficiency of the Sysmex XE-2100 analyzer for malaria. One hundred forty-four patients initially diagnosed with Plasmodium vivax infection, 319 patients with febrile illness, and 24 patients who underwent malaria treatment were analyzed…

Goesch JN, Schwarz NG, Decker ML, Oyakhirome S, Borchert LB, Kombila UD, Poetschke M, Lell B, Issifou S, Kremsner PG, Grobusch MP. Socio-economic status is inversely related to bed net use in Gabon.  Malar J. 2008 Apr 18;7(1):60 [Epub ahead of print]
Insecticide-treated bed nets (ITNs) range among the most effective measures of malaria prophylaxis, yet their implementation level in sub-Saharan Africa is still low. The goal of this study was to investigate the influence of socio-economic factors on the use of bed nets by mothers in Gabon....

April 25 has this year been declared World Malaria Day. Since 2001, April 25 has been observed as Africa Malaria Day, commemorating the signing of the historic Abuja Declaration by 44 African malaria-endemic countries at the African Malaria Summit held in 2000.

The day has been set aside on the calendar as an opportunity for malaria-free countries to learn about this age-old disease that has plagued mankind for centuries. A day for malaria afflicted countries to learn from each other’s efforts about how to control the disease.

Despite all efforts, malaria continues to be a serious public health concern throughout the world. It affects over 100 countries and approximately 40 per cent of the world s population. It causes between 300 and 500 million infections and approximately 1 million deaths each year, most of which occur in the poorest region of the world, sub-Saharan Africa. It is estimated that malaria claims a child’s life every thirty seconds and the ones who survive an episode of severe malaria are likely to suffer from learning impairment or brain damage. Pregnant women and their unborn children are also particularly vulnerable to malaria, which is a major cause of stillbirths, low birth weight and maternal anaemia.

The majority of people in this world will never experience the debilitating effects of malaria, thanks mainly to the eradication campaign adopted at the eighth annual World Health Assembly meeting in 1955. Despite the fact that the campaign was eventually abandoned and considered a failure, it registered resounding successes in wiping out malaria from large regions of the globe. Successful application of DDT as part of indoor residual spraying (IRS) programmes, coupled with the effectiveness of antimalarial treatments such as chloroquine formed cornerstones of the programme. Africa however, was largely overlooked in the global eradication effort because the continent lacked the necessary infrastructure to conduct a successful campaign.

African nations now have the tools to control the disease. Communities have effective insecticides for the targeted application on the inside of their household walls, insecticide treated bed nets, and drugs to clear the parasites from their bodies. But the obstacles to a successful control programme today are similar to those that existed during the eradication campaign — weak infrastructure, bureaucratic hurdles and the stark reality of millions of poor individuals who can barely sustain themselves, let alone spend money on personal measures to control and treat the disease.

Over the past few years, a number of large multilateral organisations have taken an interest in malaria and eradication efforts are now benefiting from more funding and more political interest. The US President’s Malaria Initiative (PMI) is set to devote $1.2 billion to malaria control in 15 African countries over 5 years, eventually benefiting an estimated 175 million people. The Global Fund for AIDS, TB and Malaria (GFATM) provides hundreds of millions of dollars to malaria prevention and treatment programmes. The US Congress is currently negotiating and authorising a bill that will seek to devote up to $9 billion for malaria control over 5 years. This interest in raising the profile of malaria must be applauded but simply pouring more money into the problem may not be sufficient to control the disease.

Without the necessary checks and balances in place this additional funding will be wasted. If the required economic development does not take place in targeted countries and a domestic commitment made to a sustainable control programme, it’s difficult to envision how the problem will be solved. There is a long, hard road to travel and, if history is anything to go by, the successful implementation of an eradication programme will have more to do with African politics and economics than with specific technologies.

In the short run, countries must continue to strive towards implementing a comprehensive malaria control programme. This implies an acute understanding of the nature of the vectors as well as the measures needed to control the parasite most effectively within each unique setting. Baseline studies in malaria affected areas need to be conducted before any interventions are initiated. Ultimately, the success of the programme should be measured in terms of reductions in morbidity and mortality, as opposed to the simplistic notion of the amount of resources expended.

Research into new and essential tools to fight malaria in Africa must continue. Desperate attention must be given to the development of a new insecticide that can be used in those areas where resistance is building up or has already built up. Furthermore, we need to remain vigilant of the quality of drugs being used to treat malaria and this involves a clamp down on the production of fake and sub-standard drugs.

World Malaria Day once again provides the opportunity to raise the profile of the disease and provide answers to the question of what works in malaria control on the ground. Additional funding is necessary but is by no means sufficient to control malaria. The necessary checks and balances must be put into place or else funding will be wasted, and World Malaria Day will be just another public relations event.

Author: Jasson Urbach is an economist with the Free Market Foundation and a director of Africa Fighting Malaria. This article may be republished without prior consent but with acknowledgement to the author. The views expressed in the article are the author s and are not necessarily shared by the members of the Foundation.

Brazil announced a new malaria treatment Thursday that scientists say offers a potentially cheap and effective way to attack a disease that largely afflicts the world s poor.

The treatment, developed by the Brazilian government in conjunction with the Drugs for Neglected Diseases Initiative, combines existing malaria drugs artesunate and mefloquine into a single, fixed-dose tablet and reduces the cost of treatment.

A key benefit is that it reduces the number of tablets patients must remember to swallow.

"Now they only need take one to two tablets a day for three days," said Bernard Pecoul, executive director of the Drugs for Neglected Diseases Initiative, an international alliance of seven health organizations.

"The fixed dose combination will probably mean greater adherence to the treatment program," said Keith Carter, regional adviser on malaria at the Pan American Health Organization, who was not involved with the treatment s development.

Carter said he had not seen the result of the Brazilian study and could not comment on it. But he noted that the World Health Organization has recommended similar combination treatments for several years and said development of a single, fixed-dose medication should make treatment easier and more effective.

Another single-dose combination is available to fight malaria, but Pecoul said this combination was more effective.

Pecoul said developers would not try to patent the new treatment because they are trying to reduce the cost of attacking a disease that mainly affects the poor.

The Brazilian government will distribute the medication, known as ASMQ, free of charge and will transfer the technology to India for production and distribution in Southeast Asia, where a full course of treatment should cost around US$2.50 (euro1.58).

A field study involving 17,000 patients in Brazil s Amazon state of Acre showed that the incidence of malaria dropped by 70 percent over a year, Pecoul said. A similar study in the Peruvian Amazon where the two drugs were used in separate doses only showed a drop of 50 percent.

Carlos Morel, one of the drug s developers and director of Brazil s Center for Developing Medical Technology at Fiocruz/Farmanginhos, said the number of patients hospitalized with malaria in the Brazilian region dropped from 2,500 to only 500 over the course of the year.

Malaria is a mosquito-borne disease caused by a parasite. The less time each person spends infected, the less likely it is to spread.

"This is really good news in a field where there hasn t been much good news lately," Morel said.

Malaria parasite secretes various proteins in infected RBC for its growth and survival. Thus identification of these secretory proteins is important for developing vaccine/drug against malaria.

The existing motif-based methods have got limited success due to lack of universal motif in all secretory proteins of malaria parasite.

Results: In this study a systematic attempt has been made to develop a general method for predicting secretory proteins of malaria parasite. All models were trained and tested on a non-redundant dataset of 252 secretory and 252 non-secretory proteins.

We developed SVM models and achieved maximum MCC 0.72 with 85.65% accuracy and MCC 0.74 with 86.45% accuracy using amino acid and dipeptide composition respectively. SVM models were developed using split-amino acid and split-dipeptide composition and achieved maximum MCC 0.74 with 86.40% accuracy and MCC 0.77 with accuracy 88.22% respectively.

In this study, for the first time PSSM profiles obtained from PSI-BLAST, have been used for predicting secretory proteins. We achieved maximum MCC 0.86 with 92.66% accuracy using PSSM based SVM model.

All models developed in this study were evaluated using 5-fold cross-validation technique.

Conclusion: This study demonstrates that secretory proteins have different residue composition than non-secretory proteins.

Thus, it is possible to predict secretory proteins from its residue composition-using machine learning technique. The multiple sequence alignment provides more information than sequence itself.

Thus performance of method based on PSSM profile is more accurate than method based on sequence composition. A web server PSEApred has been developed for predicting secretory proteins of malaria parasites (http://www.imtech.res.in/raghava/pseapred/).

Author: Ruchi Verma, Ajit Tiwari, Sukhwinder Kaur, Grish C. Varshney and Gajendra P.S. Raghava. Credits/Source: BMC Bioinformatics 2008, 9:201

Malaria, a tremendously successful pathogen that is responsible for more than 300 million cases and 1 million deaths annually, has had a large impact on the shape of the human genome. Malaria-selected mutations in human genes promote survival in areas where malaria is endemic. The parasite s substantive effect on the human genome is due to its high prevalence in areas where it is endemic and its long history of coevolution with humans. Moreover, its marked genetic diversity, generated by its sexual stage, provides the organism with many opportunities to maximally adapt to host defenses and continue transmission. In this issue of the Journal, Ayi et al.describe a polymorphism that is hypothesized to provide resistance to malaria infection.

Why is the study of pathogen-selected host polymorphisms useful? It provides insight into naturally occurring mechanisms of host defense, which could be used to develop therapeutic agents to combat disease. Often, host polymorphisms occur in multiple genes, and their combined effect on resistance to disease presents an analytical challenge that requires the development of methods that can also be applied to other complex genetic scenarios. Finally, the role of host factors needs to be considered in the evaluation of therapeutic interventions and to refine models of pathogenesis.

Defense against malaria has been ascribed to many polymorphisms that have been maintained over generations (thanks to selection) in the human genome. Such protective polymorphisms are found in disparate genes that encode the cytokine response and erythrocyte proteins. The latter class of polymorphism hits close to home for the parasite: the erythrocyte is its most remarkable niche, where it finds shelter from host defenses and abundant substrates. The mechanisms of protection from this class of polymorphism are varied, ranging from inhibiting parasite growth to compromising the ability of the parasite to adhere to the microvasculature to promoting enhanced splenic clearance before the parasite can complete its life cycle. Some studies suggest that there are additional unknown genetic polymorphisms that mediate disease outcome and that each genetic mutation accounts for a small epidemiologic effect.

The study by Ayi et al. builds on the established association between pyruvate kinase deficiency and protection from disease in a mouse model of malaria. The study shows that the extent of infection and replication of Plasmodium falciparum in vitro is significantly decreased in erythrocytes that are deficient in pyruvate kinase, as compared with that of normal human erythrocytes. Ring-stage parasites are less likely to invade pyruvate kinase–deficient erythrocytes than they are wild-type erythrocytes. Once infected, pyruvate kinase–deficient erythrocytes are more likely than wild-type cells to be cleared from the circulation by phagocytosis.

Pyruvate kinase is a glycolytic enzyme required for energy production, allowing the erythrocyte to maintain structural integrity and function. Mutations in the pyruvate kinase gene (PKLR) alter protein function, resulting in nonspherocytic hemolytic anemia. Nearly 200 different PKLR mutations are associated with pyruvate kinase deficiency; the degree of hemolysis and anemia varies markedly, depending on the mutation.

A major criticism of many genetic association studies, both in malaria and other diseases, is a lack of biologic mechanism. The study by Ayi et al., in contrast, is a study of the biologic mechanism without direct observation of an association with disease in humans. Although the biologic mechanism is considered by some to be the gold standard, testing for a genetic association would have great value. It would clinch the case for a mechanism associated with pyruvate kinase deficiency in protecting against malaria. More extensive genetic sleuthing would probably yield information about the degree of protective advantage conferred by different mutations in PKLR in different populations. The strength of protection of PKLR alleles would serve as an excellent reference by which to evaluate new alleles in other genes associated with malaria resistance, in which biologic confirmation is lacking.

More broadly, an examination of the action of selective pressure on pyruvate kinase could shed light on the history and mechanism of human resistance to malaria. Deficiency in glucose-6-phosphate dehydrogenase (G6PD), the other most common cause of nonspherocytic hemolytic anemia, also has biologic links to malaria resistance. Numerous mutations have been identified in G6PD, many of which affect the level of enzymatic activity. However, despite the considerable genetic diversity in G6PD, it appears that a single mutation that causes G6PD deficiency (approximately 12% of enzyme activity) has been selected in many African populations and is associated with malaria resistance. The study by Ayi et al. sets the stage for a case–control study to test for an association between PKLR polymorphisms and disease, as well as defining the global distribution of PKLR polymorphisms.

A new study in the April issue of the American Journal of Tropical Medicine and Hygiene, asks the question “With more than $220 million dollars dedicated to malaria treatment and prevention, why is the annual mortality rate from malaria on the rise?"

The study, entitled “Malaria Vector Management: Where Have We Come From and Where Are we Headed"” conducted by researchers from the University of Alabama at Birmingham School of Medicine, examines the current methods used to control and prevent the spread of malaria. 

Robert J. Novak, Ph.D., professor of medicine, division of infectious diseases and Ephantus J. Muturi, Ph.D., postdoctoral fellow, division of infectious diseases, who lead the study, say the millions of dollars currently being spent on malaria primarily address the mortality of pregnant women and infants. 

And, while these efforts are important and have resulted in successfully decreasing the death rate in that group with the use of bed nets and insecticides, the disease has burgeoned among teens and adults who are not being protected. 

Dr. Muturi, a Kenyan, who himself has been stricken by malaria, finds the lack of immediate attention frustrating on a more personal level. 

“I have family in Kenya who are at risk every day. Bed nets work at night and have helped contain the spread of malaria, but what about the hours when people aren’t in their beds."

The protection during the day is minimal with current insecticides that cannot be use