MALARIA: Plasmodium knowlesi in children in Malaysia

Plasmodium knowlesi can cause severe malaria in adults; however, descriptions of clinical disease in children are lacking. We reviewed case records of children (age <15 years) with a malaria diagnosis at Kudat District Hospital, serving a largely deforested area of Sabah, Malaysia, during January–November 2009. Sixteen children with PCR-confirmed P. knowlesi monoinfection were compared with 14 children with P. falciparum monoinfection diagnosed by microscopy or PCR. Four children with knowlesi malaria had a hemoglobin level at admission of <10.0 g/dL (minimum lowest level 6.4 g/dL). Minimum level platelet counts were lower in knowlesi than in falciparum malaria (median 76,500/μL vs. 156,000/mL; p = 0.01). Most (81%) children with P. knowlesi malaria received chloroquine and primaquine; median parasite clearance time was 2 days (range 1–5 days). P. knowlesi is the most common cause of childhood malaria in Kudat. Although infection is generally uncomplicated, anemia is common and thrombocytopenia universal. Transmission dynamics in this region require additional investigation.
http://www.cdc.gov/eid/content/17/5/814.htm

Artemisinin combination therapy for vivax malaria

The Lancet Infectious Diseases : Volume 10, Issue 6, June 2010, Pages 405-416 PubMed ID: 20510281
Douglas, N.M.a b , Anstey, N.M.a b , Angus, B.J.b , Nosten, F.b d e , Price, R.N.a b c
Early parasitological diagnosis and treatment with artemisinin-based combination therapies (ACTs) are key components of worldwide malaria elimination programmes. In general, use of ACTs has been limited to patients with falciparum malaria whereas blood-stage infections with Plasmodium vivax are mostly still treated with chloroquine. We review the evidence for the relative benefits and disadvantages of the existing separate treatment approach versus a unified ACT-based strategy for treating Plasmodium falciparum and P vivax infections in regions where both species are endemic (co-endemic). The separate treatment scenario is justifiable if P vivax remains sensitive to chloroquine and diagnostic tests reliably distinguish P vivax from P falciparum. However, with the high number of misdiagnoses in routine practice and the rise and spread of chloroquine-resistant P vivax, there might be a compelling rationale for a unified ACT-based strategy for vivax and falciparum malaria in all co-endemic regions. Analyses of the cost-effectiveness of ACTs for both Plasmodium species are needed to assess the role of these drugs in the control and elimination of vivax malaria.
http://www.scopus.com/record/display.url?eid=2-s2.0-77952605533&origin=inward&txGid=xIxHwce1_VFPqFnB8SYQw0y%3a2

MALARIA: Malarone in pregnancy

Amy Norton : Feb 16, 2011
NEW YORK (Reuters Health) - Pregnant women who take the anti-malarial drug Malarone during their first trimester might not be increasing their baby's risk of birth defects, a new study suggests.
Most anti-malaria drugs -- including this one -- are not approved for use in pregnancy. So when pregnant women want to travel to malaria-ridden regions, they face a huge problem: should they take preventive medicines that haven't been proven safe for the fetus?
In general, experts advise all pregnant women to avoid traveling to countries where malaria is common, since the infection itself may be dangerous to the mother and fetus.
The new study, published in the Archives of Internal Medicine, is the first to look at pregnant women's use of Malarone -- known generically as atovaquone-proguanil -- and the risk of birth defects.
So the researchers say it is too soon to declare the drug safe for the small number of pregnant women who might need to take it.
The cheapest and mostly widely used anti-malaria drug, called chloroquine, is considered safe during pregnancy. But resistance to that drug has become common worldwide.
Another anti-malaria drug, the antibiotic doxycycline, is known to have adverse effects on the fetus.
In the new study, researchers looked at data on nearly 571,000 births in Denmark between 2000 and 2008. Overall, 2 to 3 out of every 100 newborns had a birth defect.
Among the 149 women who used Malarone at some point during the first trimester, roughly one of every hundred had a baby with a birth defect.
The findings offer some reassurance that the drug is not linked to any large risk of birth defects, said lead researcher Dr. Bjorn Pasternak, of Statens Serum Institute in Copenhagen.
Still, since only a small number of women in the study took Malarone during early pregnancy, the findings cannot rule out the possibility of some risk, Pasternak said.
"We believe it is far too soon to declare this drug to be safe for use in pregnancy," he told Reuters Health in an email.
Malarone is not inexpensive -- it costs close to $200 for 24 pills. The number of pills a woman would have to take depends on how long she stays in the malaria region.
Caused by a mosquito-borne parasite, malaria is widespread (the technical term is "endemic") in large areas of Africa, Asia and South and Central America, where it kills about 1 million people a year.
An estimated 10,000 to 30,000 travelers develop malaria every year, and about 150 die.
http://www.reuters.com/article/2011/02/16/us-malaria-drug-idUSTRE71F66K20110216?feedType=RSS&feedName=healthNews

MALARIA: A Disease Close to Eradication Grows, Aided by Political Tumult in Sri Lanka

Lynsey Addario for The New York Times

By DONALD G. McNEIL Jr.: Published: December 27, 2010
 Malaria cases jumped 25 percent in Sri Lanka from 2009 to 2010, the country’s ministry of health is reporting. And while this year’s total is still small, at 580, the trend is unsettling to experts.
Sri Lanka is a bellwether for the dream of malaria eradication — and Exhibit A for the argument that politics affects the disease more than climate or public health measures do.
The country — the former British colony of Ceylon, famous for tea and cinnamon — is an island, so eradication is possible.
That almost happened once. After independence arrived in 1948, Sri Lanka had an estimated one million annual cases. With DDT and chloroquine, it drove that down to 18 cases by 1963. But spraying was cut back as DDT fell into disfavor, and by 1969, there were more than 500,000 cases.
Simultaneously, the country’s ethnic fabric fell apart. The majority Buddhist Sinhalese passed laws discriminating against the Hindu Tamils, who were favored under the British, leading to 30 years of civil war. The majority was also split for decades between pro-Soviet and pro-Western factions.
Malaria persisted, with cases highest in the north and east, where the Tamil Tiger insurgency was strongest. Nonetheless, by 2005, the country was below 2,000 cases, though experts said they were undercounted in rebel areas.
Last year, the rebellion was crushed, and malariologists hoped the new national reconciliation policy would lead to eradication. As cases ticked up, a ministry official blamed global warming — a weak argument in a wet tropical country. But he also said more clinics would be opened in former rebel areas.
http://www.nytimes.com/2010/12/28/health/28global.html?ref=health

MALARIA: Uganda Malaria Indicator Survey shows progress - is it enough?

 Bill Brieger : 14 Dec 2010

The Uganda Malaria Indicator Survey for 2009 is now available for reading. The report helpfully provides charts that distinguish levels of key indicators from the 2006 Uganda Demographic and Health Survey with the current data. While there has been clear progress, most indicators fall below the 80% targets set by the Roll Back Malaria Partnership for 2010.



The chart of the right shows that sleeping under any insecticide treated bed net the night prior to interview tripled for children under five years of age and quadrupled for pregnant women, the 2009 levels do not achieve RBM goals. Even when one looks only at households that actually possess these treated nets, one finds that use is less than ideal.



The report provides some reasons for low net usage…
The most common reason cited for non-usage was that the net was not hung (58 percent of households), especially in North East region (99 percent). Sixteen percent reported that the net was not used because it was too hot, and 11 percent said the net had too many holes or was too old.
There were also wide variations in ownership and use across different parts of the country, meaning that program managers need to look more indepth at possible regional factors that discourage access to and use of nets.
The East African countries were among the pioneers to introduce intermittent preventive treatment with sulphadoxine-pyrimethamine for pregnant women. Again we see that RBM targets are far from being met in Uganda, although progress over 2006 is evident.

16% of pregnant women got two doses in 2006
45% got one dose in 2009
32% got two doses in 2009
95% of pregnant women attended ANC with a skilled provider at least once in 2009

Clearly problems of procurement, supply and stock keeping and missed opportunities are preventing achievement of this goal.
The malaria case management picture was not cheering. Among children under five years of age with a reported fever in the two weeks before the survey …
60% took any antimalarial drug
23% of took an ACT
14% took ACT same or next day
Chloroquine and SP were still being used
Uganda is not in a unique situation. Even countries benefiting from the Global Fund, the US President’s Malaria Initiative and other major partners like Unicef, DfID and the WOld Bank are having a challenging time with managing commodities, improving service quality and attracting clients to avail themselves of malaria services.

2010 ends in 17 days. How many places will have achieved the RBM 80% targets? More importantly, what can the international partnership do to meet the needs?
http://www.malariafreefuture.org/blog/?p=1115

MALARIA: Malaria and HIV 2010

 Bill Brieger: 03 Dec 2010
Another World AIDS Day has come and passed. Sarah Boseley has commented on the information overload that comes this time of year on the disease and the range of basic health programming and valiant efforts to control it. This led to thoughts on whether there are any new developments concerning the connections between Malaria and HIV.
A quick look at the most recent PubMed listings for “Malaria AND HIV” mostly yielded sentences with the common theme of “AIDS, TB and Malaria” that considered the big disease funding efforts and the combined global burden of disease but few new insights on how each disease affects the other. Some interesting examples were uncovered.
On the biological side, Jiang and colleagues in the journal Vaccine (2010 Nov 23;28(50):7915-22) observed that, “Malaria and human immunodeficiency virus type 1 (HIV-1) infection overlap in many regions of the world.” Using mouse models they found that, “important implications for the development of a new form of bivalent vaccine against both HIV-1 and malaria.”
On the programming side, Lugada et al. examined how “Integrated disease prevention in low resource settings can increase coverage, equity and efficiency in controlling high burden infectious diseases,” in rural Kenya, and reported on a campaign that provided, “HIV counseling and testing, 60 male condoms, an insecticide-treated bednet, a household water filter for women or an individual filter for men, and for those testing positive, a 3-month supply of cotrimoxazole and referral for follow-up care and treatment.” (PLoS One. 2010 Aug 26;5(8):e12435)
Reid reported on how injections for suspected malaria cases in drug shops and stores Tanzania and other rural African settings sets the stage for HIV and other infections. The need to prevent such practices can help both diseases. (Rural Remote Health. 2010 Jul-Sep;10(3):1463)
Noting that, “Co-infection of human immunodeficiency virus (HIV) with malaria is one of the pandemic problems in Africa and parts of Asia,” Oguariri and co-investigators examined, “the impact of pyrimethamine (PYR) and two other clinical anti-malarial drugs (chloroquine [CQ] or artemisinin [ART]) on HIV-1 replication.” They showed that, “10 μM CQ and ART inhibited HIV-1 replication,” while “10 μM PYR enhanced HIV-1 replication.” This is important news for malaria case management in areas with high HIV prevalence. (Virus Res. 2010 Nov;153(2):269-76)
While these studies individually may not be earth-shaking, they do point to the continued need for partnership between Malaria and HIV control programs - common interests do exist together with the common desire to save lives.
http://www.malariafreefuture.org/blog/?p=1103

MALARIA: Nigeria: doctors directed to use ACT

The Federal Government has directed all medical doctors and other health officials in the country to henceforth start using Artemisinin-based Combined Therapy (ACT) for the treatment of malaria disease in the country.
Minister of Health, Prof. Onyebuchi Chukwu, gave the directive yesterday in Abuja during the ministerial press briefing on Affordable Medicines Facility (AMF) for malaria programme.
According to the minister, the spread of malaria had become so critical that everyone in the country was now involved.
He said: “It’s a disease everyone talks about and rightly so. In general hospitals, two-thirds of patients waiting to see the doctor are all about malaria. The launch of ACT will further accelerate our drive to ensure we have 50 per cent reduction in malaria. Thus, Nigeria had to develop another policy which includes the use of ACT.”
Chukwu also stated that the national policy does not recognize Chloroquine. For that reason, he said the government was doing all it could to phase it out.
http://nigerianbulletin.com/2010/11/30/fg-directs-doctors-on-act-for-malaria-treatment-thisday/

MALARIA: Keeping up with Malaria - 4 years and 500 postings

Bill Brieger

19 Nov 2010
This month marks the 4th year for Malaria Matters and our 500th posting. Two of our first postings we examined what happens to chloroquine when it is no longer used as a first line drug,and how malaria proposals fare at the Global Fund.
Chloroquine was valued because it was inexpensive and therefore justifiably used for presumptive treatment. Resistance showed not only that the presumptive treatment approach was likely flawed, but that single drug or mono-therapy treatments were not appropriate. Research today continues to document the spread of chloroquine resistance for example, in vivax and falciparum malaria in Indonesia.
What our 2006 posting addresses was the fact that chloroquine resistance did reduce after the drug is withdrawn as the front line treatment in Malawi. These findings were backed up by a study from Kenya published last year. The Kenya researchers reported “a reduction in resistance to CQ following official withdrawal in 1999 was found, but unlike Malawi, the decline of resistance to CQ in Kilifi was much slower,”ultimately taking twice as long as it did in Malawi - assuming use remains at a low level.
The practical research question moving into the future toward malaria elimination is whether an inexpensive drug like chloroquine can ever again find a place in the pharmacological arsenal against malaria. The experiences of both increasing and reducing drug efficacy also stress the importance of maintaining strong pharmaco-vigilence as part of any national malaria control effort.
Concerning the Global Fund we expressed disappointment in 2006 that malaria grants performed so poorly in Round 6 allocations in terms of relative proportion of total grants as well as proportion of submitted grants approved. Since that time the Roll Back Malaria Harmonization Working Group has mobilized human resources to strengthen the grant writing process. Since that time malaria grants have been gaining a greater share of total resources and have had better success in being approved.
According to AIDSPAN, this year’s Round 10 allocations may be a mixed bag for malaria. While 79% of submitted malaria proposals were recommended for approval (better than the 50% overall approval rate), only a small number of proposals were submitted (24) and ultimately approved (19) of the 89 from all sources.
This low ‘turnout’ may reflect the economic constraints at the Global Fund where there had even been some doubt earlier that a Round 10 would be issued, but it reflects poorly on the need to scale up and sustain malaria interventions into 2015 and beyond. This also does not reflect changes in Global Fund approaches such as the rolling continuation credit and the potential move toward funding based on national strategy, all of which are changes at the GFATM since 2006.
Overall once can see that in four short years the funding and technical landscape surrounding the control and elimination of malaria are changing quickly. We are closer now to a vaccine, WHO has updated its malaria treatment guidelines, long awaited rapid diagnostics tests are rolling out in larger quantities, and countries, such as those in southern Africa, that need to develop pre-elimination strategies are being identified. We intend that Malaria Matters will help you keep up with these vital changes.
http://www.malariafreefuture.org/blog/?p=1084

MALARIA: Chloroquine is again an efficacious treatment for malaria,

Laufer MK, Thesing PC, Eddington ND, Masonga R, Dzinjalamala FK, Takala SL, Taylor TE, Plowe CV.
BACKGROUND: In 1993, Malawi became the first country in Africa to replace chloroquine with the combination of sulfadoxine and pyrimethamine for the treatment of malaria. At that time, the clinical efficacy of chloroquine was less than 50%. The molecular marker of chloroquine-resistant falciparum malaria subsequently declined in prevalence and was undetectable by 2001, suggesting that chloroquine might once again be effective in Malawi.
METHODS: We conducted a randomized clinical trial involving 210 children with uncomplicated Plasmodium falciparum malaria in Blantyre, Malawi. The children were treated with either chloroquine or sulfadoxine\#8211;pyrimethamine and followed for 28 days to assess the antimalarial efficacy of the drug.
RESULTS: In analyses conducted according to the study protocol, treatment failure occurred in 1 of 80 participants assigned to chloroquine, as compared with 71 of 87 participants assigned to sulfadoxine\#8211;pyrimethamine. The cumulative efficacy of chloroquine was 99% (95% confidence interval [CI], 93 to 100), and the efficacy of sulfadoxine\#8211;pyrimethamine was 21% (95% CI, 13 to 30). Among children treated with chloroquine, the mean time to parasite clearance was 2.6 days (95% CI, 2.5 to 2.8) and the mean time to the resolution of fever was 10.3 hours (95% CI, 8.1 to 12.6). No unexpected adverse events related to the study drugs occurred.
CONCLUSIONS: Chloroquine is again an efficacious treatment for malaria, 12 years after it was withdrawn from use in Malawi. (ClinicalTrials.gov number, NCT00125489 [ClinicalTrials.gov].).

N Engl J Med. 2006 Nov 9;355(19):1959-66.

http://www.ncbi.nlm.nih.gov/pubmed/17093247

MALARIA: Chloroquine treatment of malaria banned in Ghana

October 18, 2010
Koforidua, Oct. 18, GNA - The National Malaria Control Programme (NMCP), has insisted that chloroquine has lost its efficacy for the treatment of malaria and urged the public to desist from using it for the treatment of malaria.


According to the NMCP, chloroquine now cures only 25 per cent of malaria cases treated with it, whiles the combined therapy of the artesonate amodiaquin had proved to cure 97 per cent of malaria cases.
Mr Kwame Gakpey, of the NMCP, said this in a presentation on malaria treatment, at a workshop for journalist in the Eastern Region, in Koforidua, at the weekend.
He said currently, chloroquine had been banned for the treatment of all malaria related cases in the country.
Mr Gakpey said the change from the use of chloroquine to the combined therapy of artesonate amodiaquin or coartem was backed by law, therefore any health facility using chloroquine for the treatment of malaria could be charged for breeching the law.
He said initially, because pharmacy shops and that of health facilities had a lot of stock of the chloroquine, it was allowed to phase out gradually and that by now it is expected that, the drug is out of the system.
Mr Gakpey said, although malaria was a dangerous disease, it was curable and that deaths occur from malaria because of poor management and late access to effective treatment.
Currently, statistics indicate that, 4,500 deaths occur from malaria in Ghana, including 1,500 children under five years and 60 pregnant women annually, and urged the public to be conscious of their health and insist on combined therapy treatment for malaria without any compromise.
He urged the media to use their mediums to educate the public on the ineffectiveness of chloroquine in the treatment of malaria and to alert the institutions responsible for ensuring that the drug was not imported or manufactured, "let alone sold over the counter".
According to Mr Gakpey, people were still skeptical about the ineffectiveness of chloroquine, because it might work for them, but was emphatic that the use of single drug treatment for malaria was not the best in terms of managing the disease.
http://www.blogger.com/post-create.g?blogID=3604033512937490051

MALARIA: Changes in the burden of malaria in sub-Saharan Africa

13 September 2010
The Lancet Infectious Diseases, Volume 10, Issue 8, August 2010, Pages 545-555Wendy Prudhomme O'Meara, Judith Nekesa Mangeni, Rick Steketee, Brian Greenwood

The burden of malaria in countries in sub-Saharan Africa has declined with scaling up of prevention, diagnosis, and treatment. To assess the contribution of specific malaria interventions and other general factors in bringing about these changes, we reviewed studies that have reported recent changes in the incidence or prevalence of malaria in sub-Saharan Africa. Malaria control in southern Africa (South Africa, Mozambique, and Swaziland) began in the 1980s and has shown substantial, lasting declines linked to scale-up of specific interventions. In The Horn of Africa, Ethiopia and Eritrea have also experienced substantial decreases in the burden of malaria linked to the introduction of malaria control measures. Substantial increases in funding for malaria control and the procurement and distribution of effective means for prevention and treatment are associated with falls in malaria burden. In central Africa, little progress has been documented, possibly because of publication bias. In some countries a decline in malaria incidence began several years before scale-up of malaria control. In other countries, the change from a failing drug (chloroquine) to a more effective drug (sulphadoxine plus pyrimethamine or an artemisinin combination) led to immediate improvements; in others malaria reduction seemed to be associated with the scale-up of insecticide-treated bednets and indoor residual spraying.
http://www.malarianexus.com/articles/read/80/changes-in-the-burden-of-malaria-in-sub-saharan-africa/

MALARIA: Therapeutic efficacy of chloroquine and chloroquine plus primaquine for the treatment of Plasmodium vivax in Ethiopia

02 September 2010
Plasmodium vivax is the second most important cause of morbidity in Ethiopia. There is, however, little information on P. vivax resistance to chloroquine and chloroquine plus primaquine treatment although these drugs have been used as the first line treatment for over 50 years. We assessed the efficacy of standard chloroquine and chloroquine plus primaquine treatment for P. vivax infections in a randomized open-label comparative study in Debre Zeit and Nazareth in East Shoa, Ethiopia.A total of 290 patients with microscopically confirmed P. vivax malaria who presented to the outpatient settings of the two laboratory centers were enrolled: 145 patients were randomized to receive CQ and 145 to receive CQ+ PQ treatment. Participants were followed-up for 28–157 days according to the WHO procedures. There were 12 (6.5%) lost to follow-up patients and 9 (3.1%) withdrawals. In all, 96% (277/290) of patients were analysed at day 28. Baseline characteristics were similar in all treatment groups. In all, 98.6% (275/277) of patients had cleared their parasitemia on day 3 with no difference in mean parasite clearance time between regimens (48.34±17.68, 50.67±15.70 h for the CQ and CQ+ PQ group, respectively, P = 0.25). The cumulative incidence of therapeutic failure at day 28 by a life-table analysis method was 5.76% (95% CI: 2.2–14.61) and 0.75% (95% CI: 0.11–5.2%) in the CQ and CQ+ PQ group, respectively (P = 0.19). The relapse rate was 8% (9/108) for the CQ group and 3% (4/132) for the comparison group (P = 0.07). The cumulative risk of relapse at day 157 by a life-table method was 61.8% (95% CI: 20.1–98.4%) in the CQ group, compared with 26.3% (95% CI: 7.5–29.4%) in the CQ+ PQ group (P = 0.0038).

The study confirms the emergence of CQ and PQ resistance/treatment failure in P. vivax malaria in Ethiopia. Although treatment failures were detected, they were similar between the treatment groups. We recommend regular monitoring and periodic evaluation of the efficacy of these antimalarial drugs in systematically selected sentinel sites to detect further development of resistance and to make timely national antimalarial drug policy changes.
http://www.malarianexus.com/articles/read/47/therapeutic-efficacy-of-chloroquine-and-chloroquine-plus-primaquine-for-the-treatment-of-plasmodium-vivax-in-ethiopia/

MALARIA: Can Malaria Be Beaten?

Jeremy Laurance 05 Aug 2010 The Independent
When I see a packet of malaria pills I think of that famous Clint Eastwood line from Dirty Harry, delivered as he pointed his .44 magnum at a bank robber and neither of them could remember how many shots he had fired, or whether there was still one left in the chamber. "The question you have got to ask yourself is: do I feel lucky? Well, do ya, punk?"Actually, I do. Lucky enough not to have to take the nasty, expensive little things on my periodic visits to Africa and other malarial parts of the world. Now I find myself being asked to reconsider after X Factor star Cheryl Cole's unpleasant encounter with a mosquito in Tanzania. Such is the power of celebrity.I based my view on a Lancet paper published in the 1990s by London's Hospital for Tropical Diseases which assessed the chances of contracting malaria, for those not taking prophylactic drugs, at 0.6 per cent for an average two-week holiday in East Africa. The authors described this as "high" and in public health terms I suppose it is - the Health Protection Agency points out that more than 1,500 people are diagnosed with malaria in the UK each year having acquired it abroad.But it didn't seem high to me - and I disliked the way commercial travel clinics pushed expensive injections and other protective measures at frightened travellers without quantifying the risks. So for the last 15 years I have followed a rough rule of thumb: if I am slumming it or travelling into the bush, I take the pills; if I am staying in four-star hotels in town, I don't bother. My impression is that many regular visitors to Africa do the same. Public health doctors may demur - and Ms Cole's story undoubtedly strengthens their case. She had spent only six days in Tanzania and had, reportedly, taken anti-malarial drugs that provide 90 per cent protection. How unlucky is that?Doubly unlucky because - and this is the real story about malaria - in many parts of the world it is declining, rapidly. About 2.5 billion people live in malarial areas around the globe, and the disease kills almost a million of them every year, mostly children. Changes in the incidence of the disease may go unnoticed by tourists but have huge significance for the local population. Now Cheryl Cole, who first visited Tanzania last year on a charity expedition to Mount Kilimanjaro, has helped focus attention on their plight in a way she could hardly have anticipated.In coastal Kenya, not far from where she was holidaying, cases of severe malaria in children have fallen 90 per cent in the last five years. Similar falls have been reported from other locations across Africa and the world.In certain islands in the Philippines malaria has been eliminated. Mexico is said to be close to eradication, and some countries in Central and South America are moving in the same direction. Morocco was recently declared malaria-free by the World Health Organisation, helping boost the tourist trade there.Sub-Saharan Africa, which bears 70 per cent of the disease burden, presents a much tougher challenge. Yet even here there have been spectacular advances, as in coastal Kenya. Last week, the African Leaders Malaria Alliance announced that malaria cases and deaths had been cut by up to 80 per cent in 10 African countries since 2000, including Ethiopia, Ghana, Rwanda, Zambia and Zanzibar.Among malaria specialists, where gloom prevailed a decade ago, the buzzword now is "elimination": no more malaria deaths by 2015 and no more malaria a decade or two after that. As the Lancet noted last month, "previously cautious malariologists, released from a 40-year collective depression... have been invigorated."How has this change of heart come about? Some call it the Bill Gates effect. Almost three years ago, the world's biggest philanthropist threw down a challenge to the global health community to eliminate malaria in his lifetime. Sceptics responded that his dream would only be realised if he were cryo-preserved. Yet his call had a galvanising effect.The Foundation that he leads with his wife, Melinda, has not only given grants of dizzying size to the search for a malaria vaccine, the distribution of bed nets and other measures, it has also brought a new vigour to the entire aid industry. Its speed and flexibility leaves larger bureaucracies like the UN standing, and where it goes others follow. It has been described as a new type of multilateral organisation, introducing entrepreneurial flair to a sector submerged in red tape.Some complain that Gates is seeking to replicate the world domination he achieved with Microsoft in another, albeit altruistic, sphere. These critics say the new entrepreneurial aid business he has spawned is undemocratic, overly powerful, and is leading to empire- building, wasteful competition, fragmentation and duplication. Why should Bill Gates decide which sorts of vaccines get developed? they ask.There is no denying, however, the impact of Gates's interest on the bottom line. Today's funding for malaria, from all sources, exceeds $10bn (£6.3bn) - a hundredfold increase in little more than a decade. Celebrities from Senegalese musician Youssou N'Dour to David Beckham have joined the cause. Politicians Bill Clinton and Tony Blair have become involved through their respective aid foundations, followed by a growing queue of corporate donors and public figures who bring clout, profile and funding. This week, Andrew Mitchell, the International Development Secretary, published the UK's business plan for malaria, opening a consultation on the best ways of supporting the fight against the disease.Malaria - for so long the poor relation to Aids in terms of global attention, despite claiming more lives in many countries - is suddenly glamorous.The tools for elimination are to hand. More than 200m insecticide-treated bed nets have been distributed since 2000, and are estimated to have saved 1m lives, according to the Roll Back Malaria Partnership. Ban ki-Moon, the UN Secretary General, said that with the delivery of a further 150m bed nets by the end of this year "universal coverage of malaria prevention can be achieved". Vast funds have been invested in indoor spraying against mosquitoes, in distributing more effective artemesinin-based drugs against the disease, and in developing a vaccine, with one candidate, made by the UK-based pharmaceutical manufacturer GlaxoSmithKline, in final (phase III) human trials.But meeting Gates's challenge will be a tough task. Optimists, such as Sir Richard Feachem of the Malaria Elimination Group, point to the "shrinking map" of malaria, which included the US and the UK in 1900 (when malaria was endemic in the Kent marshes). Today, 108 countries in the world are malaria-free. One hundred countries have continuing malaria transmission, and of these, 39 are embarked upon malaria elimination. The remaining 61 are striving to control malaria, but it is Feachem's hope that they too can be persuaded to switch to a policy of elimination.The task is immense. In 2008, malaria killed 863,000 people. Almost 90 per cent of those who died were in Africa, and of those, almost 90 per cent were children under five, according to the WHO. Children are especially vulnerable because they have undeveloped immune systems; the WHO estimates the disease kills 3,000 children a day.The world has been striving to eliminate malaria for more than half a century - with faint success. The Global Malaria Eradication Programme was launched in 1955 but it quickly became apparent that its ambition was not achievable in sub-Saharan Africa. In the late Sixties the strategy switched from eradication to long-term control; people with fever caused by the disease were treated with the then standard drug, chloroquine. But as resistance to the drug grew, malaria deaths rose through the 1970s and 1980s. By the early 1990s the strategy was recognised as a disaster.Throughout the 1990s, as nations wrung their hands over Aids, efforts were made to refocus attention on malaria. The world's health ministers launched a global declaration in Amsterdam in 1992 to control the disease, with a focus on Africa. The latest drive against the disease began 10 years ago, when leaders of countries across Africa signed a declaration in Abuja, Nigeria to "halve the malaria mortality for Africa's people by 2010". Initially progress was slow; there were reports that instead of declining, malaria was rising, by up to half in some areas. Accurate figures were hard to come by, and estimates were distrusted. What is not in dispute, however, is that over the last three years things have moved much more quickly, and more consistently in the right direction. The huge rise in the importation of bed nets and artemesinin drugs has saved millions of lives.Controlling malaria has come to be seen as good business, not just good charity. The disease is estimated to cost Africa $12bn a year - 1.3 per cent of its economic growth. If that sum could be saved, it would constitute the biggest boost to health and development in the continent's history. Eradicating disease boosts productivity, creates markets and stabilises governments.The future, however, is anything but certain. Though the 90 per cent fall in children with severe malaria on the Kenyan coast is impressive, the reasons are not obvious. Malaria has been in decline in this area for at least 15 years and some have suggested climate change is a factor. Meanwhile it is rising in upland areas around Mount Kenya, where incidence was previously low. Professor Robert Snow, who reported the Kenyan figures in The Lancet, said malaria had changed "from a major cause of childhood illness and death to a relatively minor problem" on Kenya's coast. But it was simplistic to attribute it to more bed nets and better drugs. "The truth is probably much more complex," he wrote.Critics also question the notion of "universal coverage" with bed nets - expected in Ethiopia and southern Sudan this year and everywhere in early 2011. How many nets can you hang in a small hut occupied by a large family? Some older children are always likely to go without. There have been distribution problems too: the rush to freight in bed nets has left thousands of them sitting in warehouses because there was no means of transporting them over the final miles.Malaria is concentrated around the equator, the "middle, wet bit" of Africa, with just seven countries accounting for two thirds of all cases: the Democratic Republic of Congo, Ethiopia, Kenya, Nigeria, southern Sudan, Tanzania and Uganda. While there have been gains in some, others such as Nigeria have done less well. With a population of 120 million, Nigeria contributes heavily to the global malaria burden.Even where success has been achieved, there is no guarantee it will be permanent. Zanzibar, the island off Tanzania that has become a luxury tourist destination, has eliminated malaria twice before but each time it has been re-imported from the mainland. Kenya has also slipped back, and in Congo the uncertainties multiply.Constant vigilance is essential. That requires stable, committed government. It is not always available. In Uganda, grants worth over $350m were suspended by the Global Fund over allegations of corruption (which are currently before the courts). In Tanzania a grant worth over $100m from the Global Fund was discovered unclaimed last year because it lacked a single signature.Countries worst affected by the disease have been reluctant to buy the new artemesinin-based drugs because of their cost. At $1 to $2 a dose, they are 10 times more expensive than chloroquine. Though funded by aid programmes today, governments wonder for how long that funding will last. There are fears about resistance too, signs of which have emerged on the Thai-Cambodian border. If the artemesinin drugs lose their potency, there is nothing else immediately in the pharmaceutical locker.Eradication may be the only way to combat resistance. The most taxing question, however, and one which divides the malaria community, is what penalties may follow success? Chris Drakeley, director of the Malaria Centre at the London School of Hygiene and Tropical Medicine, points out that enormous funds are required to eliminate the last few cases of a disease - witness polio, still defying efforts to wipe it from the planet."If malaria drops down the Top 10 list of worst diseases, what justification is there for putting in vast resources to eliminate it? In a situation where malaria had been controlled to a low level for a decade, you would have a large group of children with no immunity to the disease. The impact of an outbreak could then be devastating. There is an argument that some level of malaria is quite good - it maintains a level of immunity in the population."The best hope for the future is a vaccine. No disease has ever been eliminated without a vaccine. But malaria is not caused by a simple virus - it is an organism (a parasite) with a nucleus that is more complex than a virus.The front runner is GlaxoSmithKline's RTSS vaccine, currently being tested in 14,000 children in 11 African countries, with results due in 2012. Early trials suggested that it provided 30-50 per cent protection - far from perfect, but a lot better than nothing.Scientists are optimistic that it will provide a useful further weapon against malaria. But there will be many years yet of fighting before the war can be declared won.
http://www.independent.co.uk/life-style/health-and-families/features/can-malaria-be-beaten-2043383.html

MALARIA: Demand for malaria drug soars

03 Aug 2010 Nature
From bust to boom to bust again: artemisinin, the key ingredient of front-line antimalarial drugs, is entering the third chapter of its turbulent history. A decade ago, the compound — available only from the sweet wormwood plant Artemisia annua — was scarce and expensive. But by 2007, the market was wallowing in a surfeit of the drug as farmers flocked to grow the crop. Now, as a US$343-million initiative starts to battle malaria through hugely subsidized medicines, suppliers are again worried that there will not be enough artemisinin to go around, while farmers, plant breeders and synthetic biologists are hoping that they can snap the drug out of its roller-coaster supply cycle.This year's problems began with what should be a malaria success story. The Global Fund to Fight AIDS, Tuberculosis and Malaria last month saw its first orders for cheap drugs under its Affordable Medicines Facility — Malaria (AMFm) initiative. Using subsidies, it plans to cut the price of artemisinin-based combination therapies (ACTs), which partner artemisinin with another drug to reduce the chance of malaria parasites developing resistance, as they have done to treatments such as chloroquine.Costly convenienceGovernmental public-health clinics already offer ACTs at just $1 per dose, but roughly 60% of patients with malaria opt for convenience and buy the drugs from local market stalls and private pharmacies — even though they cost many times more. The AMFm initiative, running as a two-year trial in seven African countries and in Cambodia, hopes to ensure that even the private sector will sell ACTs at $0.20-0.50 per dose. That should improve access to the drugs, and may stop patients buying cheap but ineffective chloro­quine or the single artemisinin therapies that are promoting resistance. It will also drive up demand for artemisinin.Artemisinin suppliers have seen this all before. In 2005, the World Health Organization declared that much more of the drug was needed to increase the production of ACTs. At the time, researchers led by Jay Keasling at the University of California, Berkeley, thought that synthetic biology could solve the supply problem. They hoped to modify the genomes of bacteria and yeast to produce a precursor of artemisinin. Fermenting the organisms in huge vats could yield a plentiful and inexpensive drug supply.Keasling's semi-synthetic artemisinin project received $42.6 million over five years from the Bill & Melinda Gates Foundation, and became a focus for biotech firm Amyris of Emeryville, California, which spun out from Keasling's lab. It successfully added or tweaked a dozen genes in yeast to make artemisinic acid (D.-K. Ro et al. Nature 440, 940-943; 2006), and gave a royalty-free licence to drug firm Sanofi-aventis, headquartered in Paris, to make semi-synthetic artemisinin on a commercial scale. Four years on, the product is still two years away, says the drug company, which is scaling up production to 100,000-litre vats, financed by another $10.7-million grant from the Gates foundation, and with assistance from the Institute for OneWorld Health, a non-profit organization in San Francisco, California.While this technology was being developed, farmers in China and Vietnam planted tens of thousands of hectares of Artemisia, and by 2007 the market was swamped. The price of artemisinin plummeted from more than $1,100 per kilogram to around $200 per kilogram (see 'Boom and bust for Artemisia farmers'), putting some 80 processing companies — and untold numbers of farmers — out of business.Even though artemisinin was being sold cheaply (compared with the price that Sanofi-aventis will set in 2012), millions of people in sub-Saharan Africa were still not getting access to the ACTs. "We have learned there is a lot more to it than cost," says Jack Newman, co-founder and senior vice-president for research at Amyris. Improving access to the medicines is as important as driving down their price — hence the idea for the AMFm, and its focus on the local businesses that sell treatments.If farmers grew enough Artemisia before, why not again? With food prices rising, the incentive to plant the crop this time is low, notes Malcolm Cutler, an artemisinin-industry expert and director of the consultancy FSC Development Services, near Gloucester, UK. His priority is to improve communication between growers, processors and drug companies, and to help farmers who must decide to plant Artemisia 14 months before that crop's drug will be produced.This year, the Assured Artemisinin Supply System (A2S2) initiative, supported by the international drug-purchasing facility UNITAID, began to give advance loans to the companies that extract artemisinin from plants, and to encourage drug firms to sign long-term contracts with them. About 10,000 hectares of Artemisia was planted this year, twice as much as in 2009. But recent floods in China and Vietnam, and a drought in East Africa, mean that yields of artemisinin for use in 2011 may be only two-thirds of what has been planted, says Cutler.Breeding boostYields could be vastly improved by planting new Artemisia strains. On average, one kilogram of its dried leaves yields some 8 grams of artemisinin. But at the National Institute of Agricultural Botany in Cambridge, UK, researchers have used selective breeding to create hybrid plants that produce up to 24 grams, says Colin Hill, chair of an Artemisia breeding consortium supported by the UK Department for the Environment, Food and Rural Affairs. These plants are now being grown and harvested commercially in Madagascar, and trialled in South Africa, Uganda, Zimbabwe and the United States, as well as in Britain.In an alternative approach, Ian Graham and colleagues at the University of York, UK, identified key Artemisia genes that could optimize agricultural yields, robustness or other desirable traits when the plant is grown in different areas of the globe (I. A. Graham et al. Science 327, 328-331; 2010). Graham says that the work has helped to create plants that produce up to 50% more artemisinin per kilogram of leaves than the best commercial variety. They expect to release seed to commercial growers in mid-2012.Despite the advances in plant bio­technology, Keasling says that semi-synthetic artemisinin is still sorely needed. Although it began as a way to make the drug more cheaply, the mass-produced semi-synthetic will be no cheaper than the plant-derived version — partly because Sanofi-aventis does not want to undercut farmers. Instead, it will be used to smooth out the cycle of boom and bust in crop-based artemisinin supply. "A stable and adequate source of artemisinin would be fundamentally important," says Silvia Schwarte of the World Health Organization's malaria programme.As Newman says: "If you suddenly need twice as much artemisinin, you just fire up another fermenter.
"http://www.nature.com/news/2010/100804/full/466672a.html
http://www.fightingmalaria.org/news.aspx?id=1486

MALARIA: Therapeutic efficacy of chloroquine and chloroquine plus primaquine for the treatment of Plasmodium vivax in Ethiopia

30 July 2010
Plasmodium vivax is the second most important cause of morbidity in Ethiopia. There is, however, little information on P. vivax resistance to chloroquine and chloroquine plus primaquine treatment although these drugs have been used as the first line treatment for over 50 years. We assessed the efficacy of standard chloroquine and chloroquine plus primaquine treatment for P. vivax infections in a randomized open-label comparative study in Debre Zeit and Nazareth in East Shoa, Ethiopia.A total of 290 patients with microscopically confirmed P. vivax malaria who presented to the outpatient settings of the two laboratory centers were enrolled: 145 patients were randomized to receive CQ and 145 to receive CQ+ PQ treatment. Participants were followed-up for 28–157 days according to the WHO procedures. There were 12 (6.5%) lost to follow-up patients and 9 (3.1%) withdrawals. In all, 96% (277/290) of patients were analysed at day 28. Baseline characteristics were similar in all treatment groups. In all, 98.6% (275/277) of patients had cleared their parasitemia on day 3 with no difference in mean parasite clearance time between regimens (48.34±17.68, 50.67±15.70 h for the CQ and CQ+ PQ group, respectively, P = 0.25). The cumulative incidence of therapeutic failure at day 28 by a life-table analysis method was 5.76% (95% CI: 2.2–14.61) and 0.75% (95% CI: 0.11–5.2%) in the CQ and CQ+ PQ group, respectively (P = 0.19). The relapse rate was 8% (9/108) for the CQ group and 3% (4/132) for the comparison group (P = 0.07). The cumulative risk of relapse at day 157 by a life-table method was 61.8% (95% CI: 20.1–98.4%) in the CQ group, compared with 26.3% (95% CI: 7.5–29.4%) in the CQ+ PQ group (P = 0.0038). The study confirms the emergence of CQ and PQ resistance/treatment failure in P. vivax malaria in Ethiopia. Although treatment failures were detected, they were similar between the treatment groups. We recommend regular monitoring and periodic evaluation of the efficacy of these antimalarial drugs in systematically selected sentinel sites to detect further development of resistance and to make timely national antimalarial drug policy changes.
http://www.malarianexus.com/articles/read/47/therapeutic-efficacy-of-chloroquine-and-chloroquine-plus-primaquine-for-the-treatment-of-plasmodium-vivax-in-ethiopia

MALARIA: Epidemiology of drug-resistant malaria

Since the first reports of chloroquine-resistant falciparum malaria in southeast Asia and South America almost half a century ago, drug-resistant malaria has posed a major problem in malaria control. By the late 1980s, resistance to sulfadoxine-pyrimethamine and to mefloquine was also prevalent on the Thai-Cambodian and Thai-Myanmar (Thai-Burmese) borders, rendering them established multidrug-resistant (MDR) areas. Chloroquine resistance spread across Africa during the 1980s, and severe resistance is especially found in east Africa. As a result, more than ten African countries have switched their first-line drug to sulfadoxine- pyrimethamine. Of great concern is the fact that the efficacy of this drug in Africa is progressively deteriorating, especially in foci in east Africa, which are classified as emerging MDR areas. Urgent efforts are needed to lengthen the lifespan of sulfadoxine-pyrimethamine and to identify effective, affordable, alternative antimalarial regimens. Molecular markers for antimalarial resistance have been identified, including pfcrt polymorphisms associated with chloroquine resistance and dhtr and drips CIhPS polymorphisms associated with sulfadoxine-pyrimethamine resistance. Polymorphisms in pfmdr1 may also be associated with resistance to chloroquine, mefloquine, quinine, and artemisinin. Use of such genetic information for the early detection of resistance foci and future monitoring of drug-resistant malaria is a potentially useful epidemiological tool, in conjunction with the conventional in-vivo and in-vitro drug-sensitivity assessments. This review describes the various features of drug resistance in Plasmodium falciparum, including its determinants, current status in diverse geographical areas, molecular markers, and their implications.

http://www.scopus.com/record/display.url?eid=2-s2.0-0036242351&origin=inward&txGid=570t1pj4m6HLiuI3ulhvnph%3a2

MALARIA: drug resistance

The World Health Organisation, governments, and non-profit groups are not paying enough attention to the dangers of drug-resistant drugs, a report from the Centre for Global Development has warned.
According to the report, laudable efforts to increase access to drugs in the developing world are hardly accompanied by measures to protect the continued effectiveness of drug treatment.
It called on the distributing agency to “strenuously enforce quality standards throughout the supply chain, ensure that adequate knowledge is gathered about the effectiveness of the medicines they are providing, and use their purchasing power to drive drug quality standards throughout the supply chain.”
The report, which was released on Tuesday, added that children in the developing world die every year from drug-resistant strains of malaria, tuberculosis, AIDS, and other diseases.
It also revealed that more than 40 percent of children worldwide live in malaria endemic countries, while malaria kills almost 1 million children under the age of five in sub-Saharan Africa alone annually.
Many of the drug distribution programmes may be driving drug resistance and endangering the lives they are meant to save, according to the report from the Centre for Global Development.
“We are rapidly losing our ability to cure an alarming number of the most serious and common diseases of the developing world because of an invisible adversary: drug resistance. Resistance is inevitable - but careless practices in drug supply and use are hastening it unnecessarily.
“Without an immediate global effort to safeguard lasting treatment effectiveness, drug resistance will quickly become a widespread threat, claiming lives, raising the cost of curing patients, and making future generations increasingly vulnerable to deadly diseases that were easily cured in the past, ” said the Centre’s Rachel Nugent, who led the group that wrote the report.
High cost
Since 2006, donors have spent more than 1.5 billion dollars on specialised drugs to treat resistant bacteria and viruses, and this could worsen the report cautions.
The Centre’s report looks for even broader action, urging WHO to lead others, including pharmaceutical companies, governments, philanthropies that buy and distribute medicines, hospitals, healthcare providers, pharmacies and patients.
The report finds clear links between increased drug availability and resistance. For instance, in countries with the highest use of antibiotics, 75 to 90 percent of Streptococcus pneumoniae strains are drug-resistant, it found.
“Poor quality drugs, counterfeit drugs, incomplete use of drugs, and other factors all contribute to the problem, and this problem will worsen as drug access programs succeed,” it cautions.
“The number of people being treated for HIV/AIDS, for example, increased 10-fold between 2002 and 2007; there was an 8-fold rise in deliveries of (drugs) for malaria treatment between 2005 and 2006.
“And the Stop TB Partnership’s Global Drug Facility has expanded access to drugs for TB patients, offering nearly 14 million patient treatments in 93 countries since 2001,” it added.
Child’s health impact
The long-term effects of malaria on a child’s health and development are often insufficiently recognised and poorly managed, the report identifies.
“A severe form of the disease, cerebral malaria, kills 10-20 percent of those children it affects, while an additional 7 percent are left with permanent neurological problems, including blindness, epilepsy, and speech and learning difficulties.
“Chloroquine was an effective first-line malaria treatment for more than 50 years, but when resistance rates became unacceptably high in the mid-1990s, SP became the only affordable, effective alternative with limited side effects,” it stated.
Mrs. Nugent, who is also the deputy director of global health, while commenting on drug resistance and the administering of bad malaria pills in some Africa countries, told journalists in February 2010, that, “there are many cases of malaria that are being only partially treated, and that just guarantees acceleration of artemisinin drug resistance.”
The result of a study conducted in Africa then revealed that high rates of the most effective type of malaria-fighting drugs sold in three African countries are poor quality - including nearly half the pills sampled in Senegal.
The group, however, highlighted the need for governments to “have a responsibility to provide regulation and oversight of drug licensing, manufacturing distribution, and use, as well as to properly support laboratory facilities and surveillance systems, in order to detect and monitor drug efficacy.”
Patients, prescribers, and dispensers were all advised to gain greater awareness of the personal and social costs of drug resistance, and employ far greater diligence in appropriately using drugs.
http://234next.com/csp/cms/sites/Next/Home/5581274-146/global_drug_resistance_raises_fear_says.csp

MALARIA: Haiti

Recent calls to eliminate malaria from Hispaniola — the last Caribbean island with endemic transmission of Plasmodium falciparum — are timely and important, write Joseph Keating, Donald Krogstad and Thomas Eisel from Tulane University in the United States in The Lancet Infectious Diseases.
It would provide proof of principle that malaria elimination is possible in complex environments. But elimination is also needed because there is now evidence of chloroquine resistance in Haiti and fast action is needed before the country is forced to switch to a more expensive combination therapy.
Lessons learnt in Haiti will be critical for informing other countries seeking malaria elimination. If elimination cannot be achieved on this small Caribbean island, there is little hope that it can be achieved in Sub-Saharan Africa where the malaria burden is higher and its control more complicated, say the authors.
But they add that elimination strategies used on the island should not be oversimplistic adaptation of control measures used in Africa or other endemic areas.
The key to eliminating malaria in Hispaniola lies in using a combination of methods to eliminate the parasite reservoir in human beings, prevent transmission and mobilise the community to seek out diagnosis and treatment.
All this requires unshakeable political will.
The cost of eliminating malaria in Hispaniola may be high — but it would set a precedent for health diplomacy and is a prerequisite to any global malaria elimination campaign.
http://www.scidev.net/en/opinions/why-we-must-eliminate-malaria-from-hispaniola.html

MALARIA: Historical aspects

Kicking off proceedings was LSHTM’s Professor Brian Greenwood, a legend in malaria research, who painted a picture of how malaria treatment used to be – and how much it has changed.
Forty years ago almost every African child had malaria, with an estimated prevalence of 95 per cent (though Greenwood reckoned it was nearer to 100 per cent in reality). Yet, at the time, confidence in malaria treatments was high. The front-line anti-malaria drugs such as chloroquine were effective and anti-malarials for prophylaxis were widely sold. “We didn’t have seminars about malaria,” said Greenwood, “People didn’t feel there needed to be [any]”.
But that was before the spectre of anti-malaria drug resistance emerged. Following the first report in 1968, resistance spread rapidly through the continent, rendering many of the front-line treatments ineffective and forcing a major rethink of treatment strategies.
A serious barrier was changing doctors’ behaviour. Despite the fact that resistance was widely acknowledged, chloroquine continued to be (mis-)used. Why?
“Everyone liked chloroquine,” said Greenwood, “Doctors had confidence in it from years of effective use, and doctors are very conservative by nature. Getting them to change their minds was a hard task.”
Moreover, chloroquine had benefits beyond malaria. It is an effective anti-inflammatory, one of the reasons the drug was always prescribed, even if the patient didn’t have malaria. Said Greenwood, “It was thought to be fine to do so as they were always likely to benefit”.
Furthermore, there was a widespread (erroneous) belief that having a few parasites circulating in the body ‘stimulated the immune system’. It was common practice in many places to give patients just one day of a three-day course of chloroquine.
We now know that many of these practices are detrimental to health and a boon to increasing the resistance of the parasite to the drug. The patient could develop anaemia or the parasite could recover and cause another bout of malaria.
By the 1990s the malaria community had learnt that treatment should eliminate all parasites. This was in no small part due to pioneering research by scientists such as Professor Nick White from the Wellcome Trust’s Major Overseas Programme in Thailand (in South-east Asia the idea of leaving parasites around for immunity was never fully accepted). Also, from treating tuberculosis, researchers and healthcare workers soon realised that the use of mono-therapies – and overuse of them at that – was helping to increase drug resistance.
We now know the importance of diagnosing and only treating those who really have malaria, yet the relative slowness with which the community recognised these dangers was disastrous. Even today the idea of leaving a few parasites in the body has not completely been dispelled. As Greenwood said, it’s taken a long time to learn those messages and we are mostly there now, but the message must continue to be broadcast.
http://wellcometrust.wordpress.com/2010/04/26/counting-malaria-out-malaria-treatment-as-it-used-to-be/

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?