MALARIA: WHO World Malaria Report for 2010

Summary
The World Malaria Report 2010 summarizes information received from 106 malaria-endemic countries and other partners and updates the analyses presented in the 2009 Report. It highlights continued progress made towards meeting international targets for malaria control to be achieved by 2010 and 2015. The report outlines the evolving situation of financing for malaria control, how these growing resources have resulted in increased coverage of WHO-recommended malaria control interventions, and the association between this
rapid scale-up and substantial reductions in malaria burden.

International funding for malaria control has risen steeply in the past decade. Disbursements reached their highest ever levels in 2009 at US$ 1.5 billion, but new commitments for malaria control appear to have stagnated in 2010, at US$ 1.8 billion. Countries with smaller populations at risk continue to receive more funding per person at risk than more populous countries. The amounts committed to malaria, while substantial, still fall short of the resources required for malaria control, estimated at more than US$ 6 billion for the year 2010.

The increased financing has resulted in tremendous progress in increasing access to insecticide-treated mosquito nets (ITNs) in the past 3 years. By the end of 2010, approximately 289 million ITNs will have been delivered to sub-Saharan Africa, enough to cover 76% of the 765 million persons at risk of malaria. It is estimated that 42% of households in Africa owned at least one ITN in mid-2010, and that 35% of children slept under a ITN. The percentage of children using ITNs is still below the WHA target of 80% partly because up to the end of 2009, ITN ownership remained low in some of the largest African countries. Low rates of use reported in some surveys are primarily due to a lack of sufficient nets to cover all household members; household survey results suggest that most (80%) of the available ITNs are used.

While the rapid scale-up of ITN distribution in Africa represents an enormous public health achievement, it also represents a formidable challenge for the future in ensuring that the high levels of coverage are maintained. The lifespan of a long-lasting ITN is currently estimated to be 3 years. Nets delivered in 2006 and 2007 are therefore already due for replacement, and those delivered between 2008 and 2010 soon will be. Failure to replace these nets could lead to a resurgence of malaria cases and deaths.

IRS programmes have also expanded considerably in recent years, with the number of people protected in sub-Saharan Africa increasing from 13 million in 2005 to 75 million in 2009, corresponding to protection for approximately 10% of the population at risk in 2009.

Current methods of malaria vector control are highly dependent on a single class of insecticides, the ethroids, which are the most commonly used compounds for IRS and the only insecticide class used for ITNs. The widespread use of a single class of insecticide increases the risk that mosquitoes will develop resistance, which could rapidly lead to a major public health problem. The risk is of particular concern in Africa, where insecticidal vector control is being deployed with unprecedented levels of coverage and where the burden of malaria is greatest.

WHO now recommends that all cases of suspected malaria be confirmed with a diagnostic test prior to treatment. As the incidence of malaria decreases through much of sub-Saharan Africa, the need to differentiate malaria from non-malarial fevers becomes more pressing. The proportion of reported cases in Africa confirmed with a diagnostic test has risen substantially from less than 5% at the beginning of the decade to approximately 35% in 2009, but low rates persist in the majority of African countries and in a minority of countries in other regions. A small number of countries have shown that it is possible to scale up rapidly the availability of malaria diagnostic testing on a national scale, provided that attention is given to adequate preparation, training, monitoring, supervision and quality control. Such experiences have been linked with large savings in the use of artemisinin-based combination therapies (ACTs) and with improved malaria veillance.

Information from manufacturers indicates that the number of ACTs procured has increased in every year since 2005. By the end of 2009, 11 African countries were providing sufficient courses of ACTs to cover more than 100% of malaria cases seen in the public sector; a further 8 African countries delivered sufficient courses to treat 50%–100% of cases. These figures represent a substantial increase since 2005, when only 5 countries were providing sufficient courses of ACT to cover more than 50% of patients treated in the public
sector. However, information on access to treatment is generally incomplete, particularly for the significant proportion of patients treated in the private sector.

The use of oral artemisinin-based monotherapies threatens the therapeutic life of ACTs by fostering the spread of resistance to artemisinins. By November 2010, 25 countries were still allowing the marketing of these products and 39 pharmaceutical companies were manufacturing them. Most of the countries that still allow the marketing of monotherapies are located in the African Region and most of the manufacturers are in India. The spread of resistance to antimalarial medicines over the past few decades has led to an intensification of efficacy monitoring to allow early detection of resistance. Despite the observed changes in parasite sensitivity to artemisinins, the clinical and parasitological efficacy of ACTs has not yet been compromised, even in the Greater Mekong sub-region. Nonetheless, both components of the drug combination are currently at risk and using an ACT with an ineffective partner medicine can increase the risk of development or spread of artemisinin resistance.

A total of 11 countries and one area in the WHO African Region showed a reduction of more than 50% in either confirmed malaria cases or malaria admissions and deaths in recent years. A decrease of more than 50% in the number of confirmed cases of malaria between 2000 and 2009 was found in 32 of the 56 malaria-endemic countries outside Africa, while downward trends of 25%–50% were seen in 8 other countries. Morocco and Turkmenistan were certified by the Director-General of WHO in 2009 as having eliminated malaria.

In 2009, the European Region reported no cases of P. falciparum malaria for the first time. It is estimated that the number of cases of malaria rose from 233 million in 2000 to 244 million in 2005 but decreased to 225 million in 2009. The number of deaths due to malaria is estimated to have decreased from 985 000 in 2000 to 781 000 in 2009. Decreases in malaria burden have been observed in all WHO Regions, with the
largest proportional decreases noted in the European Region, followed by the Region of Americas. The largest absolute decreases in deaths were observed in Africa.

While progress in reducing the malaria burden has been remarkable, there was evidence of an increase in malaria cases in 3 countries in 2009 (Rwanda, Sao Tome and Principe, and Zambia). The reasons for the resurgences are not known with certainty. The increases in malaria cases highlight the fragility of malaria control and the need to maintain control programmes even if numbers of cases have been reduced substantially. The experiences in Rwanda and Zambia also indicate that monthly monitoring of disease surveillance data, both nationally and subnationally, is essential. Since many countries in sub-Saharan Africa had inadequate data to monitor disease trends, it is apparent that greater efforts need to be made to strengthen routine surveillance systems. Major epidemiological events could be occurring in additional countries without being detected and investigated.

MALARIA: Cambodia: Malaria Drug Resistance in Cambodia Not a Surprise

Health officials in Cambodia have found a strain of malaria that's showing resistance to the main anti-malaria drug, known as artemisinin.Resistance means patients can take longer to recover. Health officials and medical aid groups in Africa - home to most of the world's malaria cases - are keeping a close eye on the situation in Cambodia.One of the groups battling the disease is Africa Fighting Malaria. Director Richard Tren says news of the drug resistance in Cambodia did not come as a surprise."It's not new news. This is something people have been concerned about for some time. In that part of Southeast Asia, the artemisinin-class of drugs has been used for a long time. They've been used as a mono-therapy. In other words, they haven't been combined with other drugs," he says.Long-term use of a single drug to treat malaria leads to drug resistance, according to Tren."This has been the history of malaria treatment. The good part is that the authorities are trying to do something about it. This is not being ignored."What can be done?One of the steps being taken is improving drug treatment policies."They're making sure that malaria treatment is done with combination therapies so that you're mixing the artemisinin drug with a different drug that has a different mode of action. What happens then if there is resistance to the artemisinin, the other drug will take that parasite out," says Tren.But drugs alone won't solve the malaria problem, no matter how effective. Transmission of the malaria parasite must be sharply reduced."If there are fewer cases of malaria, Tren says, "reduced transmission means that the resistant gene of the malaria parasite can't be drive through a population. Reducing malaria burden and improving treatment is the only way that we have to control this."He warns though, that the situation in Cambodia is very serious because "there's no next class of drug of the artemisinin-based class of drugs. They're our last, best hope of malaria treatment and it will be many years before we get a new class of drug available."Worse in Africa, but...Most of the one million malaria deaths each year occur in Africa."The burden of malaria in Africa is much higher. There is a much more deadly strain of malaria. The falciparum malaria that you get in Africa is much more likely to kill. And unfortunately, you see the problems that you do in Southeast Asia, where you have ongoing use of these mono-therapy drugs," he says.Africa Fighting Malaria research found a high rate of "sub-standard" and fake medicines being sold on the continent in private markets."We have to be clear that no drug resistance has been found in Africa yet. These artemisinin drugs are still highly effective, but it is something we have to be very vigilant about," he says.While mono-therapy is found in Africa, official policies call for a different approach."Officially, all governments are supposed to be using the combination therapies. But the reality is in many African settings people buy their medicines from shops and kiosks and the mono-therapies are still being used far too much. African leaders, African governments have committed themselves to getting these mono-therapies off the market," he says.The more mono-therapy is used in Africa, the greater the risk of artemisinin resistance.A vaccineA malaria vaccine would help but not solve the epidemic."We're closer now than ever before," Tren says, "with a good candidate vaccine that is being supported by the Gates Foundation and by the drug company GSK (GlaxoSmithKline) and other partners."But he warns that a malaria vaccine would not be as effective as a smallpox vaccine, for example. "This will reduce the probability of dying by about half, I think. You know, this is not going to be a magic bullet,' he says.Effective medicines and malaria control will still be needed, including insecticide treated bed nets and indoor spraying of homes with insecticides to control mosquitoes.
http://www1.voanews.com/english/news/health/decapua-africa-malaria-drug-6jul10-97862634.html

MALARIA: Molecular Markers to identify drug resistance

Effective monitoring strategies are needed to reduce the malaria burden in tropical and subtropical areas. Molecular markers for drug resistance represent a great tool for evaluating drug efficacy and guiding treatment policy. Molecular markers for resistance are based on genetic changes that confer parasite resistance to drugs. To date, their validation process had been slow and their application as surveillance of resistance has been limited.
Development and Validation of Molecular Markers for Resistance
In the late 20th century, candidate molecular markers for antimalarial drug resistance were identified by cloning and sequencing parasite homologues of genes that mediate resistance in other organisms and by using reverse genetics approaches to analyse the progeny of genetic crosses between sensitive and resistant parasites.
Differences in DNA sequence or gene expression between sensitive and resistant parasites were described, and point mutations, differences in length repeat sequences or copy number were evaluated for associations with in vitro resistance phenotypes.
Finally, molecular markers for resistance were assessed in ecological studies and clinical trials to establish their association with treatment outcome in vivo. Other factors such as acquired immunity and pharmacokinetics influence the clearance of the parasite rendering challenging the evaluation of molecular markers.
Molecular Markers for Resistance to Monotherapy
Until recently, conventional drugs to treat malaria were chloroquine and the antifolates, sulphadoxine and pyrimethamine. Unfortunately, reliable markers for chloroquine and sulphadoxine-pyrimethamine (SP) resistance were established only after resistance to these drugs was widespread.

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Chloroquine resistance has been linked to polymorphisms in the chloroquine resistance transporter (PfCRT), and mutations in the P-glycoprotein homologue (Pgh1) encoded by pfmdr1 modulate this resistance. Pyrimethamine resistance is conferred by polymorphisms in the parasite dihydrofolate reductase (DHFR) and polymorphisms in dihydropteroate synthase (DHPS) cause resistance to sulphadoxine.
Application of Resistance Markers
Routine assessment of drug resistance using molecular markers is not yet a reality and only a few molecular surveys have been conducted. Nevertheless, the direct practical value of molecular surveys came from outbreak of malaria in 1999 in Mali. Molecular assays for markers predictive of resistance to chloroquine and SP suggested an unexpectedly high prevalence of resistance to chloroquine, but not to SP. Consequently, the population was effectively treated with SP. Another example came from Tanzania where molecular markers for resistance had been used to guide national treatment policy.
Resistance markers have also predicted the return of susceptible parasites after the removal of drug pressure. In Malawi, a decrease in the prevalence of the molecular marker for chloroquine resistance and an increase in the prevalence of SP markers were detected soon after the country switched from chloroquine to SP for the first line therapy of malaria. These data were confirmed by a clinical trial showing a dramatic increase in chloroquine efficacy an equally dramatic decrease in SP efficacy.
Molecular Markers for Resistance in the ACT Era
In the era of artemisinin-based combination therapies (ACTs), tracking resistance will be crucial to prolong the therapeutic lives of these new drugs. ACT associate artemisinins with other antimalarials such as amodiaquine, lumefantrine, and piperaquine. To date, the molecular basis for their resistance is not well established. Recent advances in genomic technologies should help identifying and validating markers as soon as resistance emerges.Read more at Suite101: Malaria: Molecular Markers for Drug Resistant Falciparum parasite http://biotechpharmaceuticals.suite101.com/article.cfm/malaria-molecular-markers-for-drug-resistant-falciparum-parasite#ixzz0oqYN4rbd

MALARIA: Problems in practical therapy

Despite the widespread availability of effective new drugs and diagnostic tools, malaria still poses a risk to half the world’s population, and each year about a million people die of the disease, heard a seminar held at the London School of Hygiene and Tropical Medicine to mark world malaria day on 25 April.
The United Nations has called for universal provision of insecticide treated bed nets and prompt treatment for all people at risk of malaria by the end of this year, to achieve the goal of near zero deaths by 2015.
Yet major problems remain. Issues such as misdiagnosis and overprescription of treatments, counterfeit drugs, problems in supply and delivery, and emerging resistance to drugs "all hamper effective treatment." A lack of awareness among donors and the public of some these basic problems "threaten the success of global malaria control efforts."
Brian Greenwood, professor of clinical tropical medicine at the London School of Hygiene and Tropical Medicine, pointed out that treating malaria 40 years ago was much easier, as virtually every child in rural Africa had parasites in their blood, and treatments were cheap and effective. Nowadays prevalence was down to 5-10%, making it necessary to pick out those who needed treatment. Doctors had also failed to appreciate the danger of reliance on monotherapy, which had led to widespread resistance to chloroquine, making it essential to find effective new combination treatments.
Chris Whitty, head of research at the UK Department for International Development, said that these days "almost every death from malaria is an avoidable tragedy." The roll-out of effective new artemisinin based combination therapies meant that the disease was easily treatable, yet for various complex reasons people aren’t getting the drugs they need. Many people fail to seek care, many receive treatment in the informal sector, and many don’t get effective antimalarials.
Most people with malaria are poor, he said, and unable to afford the indirect costs of formal health care, meaning that many people still bought cheaper, less effective drugs from the private sector. Existing drugs are cheap but ineffective, while effective drugs are not cheap.
David Bell of the World Health Organization said that the development of rapid diagnostic tests showed that only about a quarter of cases of fever were actually malaria and that more than 50% of those treated for symptoms of malaria did not actually have the disease.
In Africa over half of cases of malaria were diagnosed on symptoms, not tests. Mr Bell emphasised that without parasite based diagnosis most recipients of artemisinin based combination therapies would not have malaria, which meant not just a waste of scarce resources but also that non-malarial febrile illness went undiagnosed and untreated. The roll-out of new diagnostics has left a problem of how to treat non-malarial fevers. It was essential to build effective programmes, not just to fund procurement, he said.
Shunmay Yeung, senior lecturer in health economics and policy at the London School of Hygiene and Tropical Medicine, described the alarming development of resistance to artemisinin in Cambodia. She said that the resistance was only to artemisinin, not to combination therapies that include artemisinin derivatives, which underlined the need for combination rather than monotherapies.
The problem of counterfeit and substandard drugs was discussed by Paul Newton, reader in tropical medicine at Oxford University, who emphasised the need to differentiate between the two as they had different causes and solutions. Although substandard drugs were an issue of quality assurance, counterfeits were the work of criminal gangs which required a concerted effort by Interpol. Counterfeit drugs were already "an under-appreciated public health disaster" in Asia and now posed a tremendous threat in Africa, he said.
http://www.bmj.com/cgi/content/full/340/apr27_3/c2295?