MALARIA: Global report on antimalarial efficacy and drug resistance: 2000-2010

Global report on antimalarial efficacy and drug resistance: 2000-2010


Authors: WHO; Publication date: 2010; Languages: English; ISBN: 9789241500470



Overview
This report provides a comprehensive, global overview of antimalarial drug efficacy and the resistance of malaria parasites to the antimalarial medicines used between 2000 and June 2010. Policy-makers in national ministries of health will benefit from this document, as it provides both a global and a regional picture of the efficacy of the antimalarial medicines currently used in national treatment programmes. In addition, the report will be a reference for scientists, enhancing their understanding of the complexity of antimalarial drug resistance.
http://www.who.int/malaria/publications/atoz/9789241500470/en/index.html

MALARIA: Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial

Frank Smithuis et al
09 Sep 2010
The Lancet Infectious Diseases
Background
Artemisinin-combination therapy (ACT) is recommended as first-line treatment of falciparum malaria throughout the world, and fixed-dose combinations are preferred by WHO; whether a single gametocytocidal dose of primaquine should be added is unknown. We aimed to compare effectiveness of four fixed-dose ACTs and a loose tablet combination of artesunate and mefloquine, and assess the addition of a single gametocytocidal dose of primaquine.
Methods

In an open-label randomised trial in clinics in Rakhine state, Kachin state, and Shan state in Myanmar (Burma) between Dec 30, 2008, and March 20, 2009, we compared the effectiveness of all four WHO-recommended fixed-dose ACTs (artesunate—mefloquine, artesunate—amodiaquine, dihydroartemisinin—piperaquine, artemether—lumefantrine) and loose artesunate—mefloquine in Burmese adults and children. Eligible patients were those who presented to the clinics with acute uncomplicated Plasmodium falciparum malaria or mixed infection, who were older than 6 months, and who weighed more than 5 kg. Treatments were randomised in equal numbers within blocks of 50 and allocation was in sealed envelopes. All patients were also randomly assigned to receive either a single dose of primaquine 0·75 mg base/kg or not. Patients were followed up for 63 days. Treatment groups were compared by analysis of variance and multiple logistic regression. The primary outcome was the 63 day recrudescence rate. This study is registered with clinicaltrials.gov, number NCT00902811.

Findings

155 patients received artesunate—amodiaquine, 162 artemether—lumefantrine, 169 artesunate—mefloquine, 161 loose artesunate—mefloquine, and 161 dihydroartemisinin—piperaquine. By day 63 of follow-up, 14 patients (9·4%; 95% CI 5·7—15·3%) on artesunate—amodiaquine had recrudescent P falciparum infections, a rate significantly higher than for artemether—lumefantrine (two patients; 1·4%; 0·3—5·3; p=0·0013), fixed-dose artesunate—mefloquine (0 patients; 0—2·3; p<0·0001), loose artesunate—mefloquine (two patients; 1·3%; 0·3—5·3; p=0·0018), and dihydroartemisinin—piperaquine (two patients 1·3%; 0·3—5·2%; p=0·0012). Hazard ratios for re-infection (95% CI) after artesunate—amodiaquine were 3·2 (1·3—8·0) compared with the two artesunate—mefloquine groups (p=0·01), 2·6 (1·0—6—0) compared with artemether—lumefantrine (p=0·04), and 2·3 (0·9—6·0) compared with dihydroartemisinin—piperaquine (p=0·08). Mixed falciparum and vivax infections were common: 129 (16%) had a mixed infection at presentation and 330 (41%) patients had one or more episodes of Plasmodium vivax infection during follow-up. The addition of a single dose of primaquine (0·75 mg/kg) reduced P falciparum gametocyte carriage substantially: rate ratio 11·9 (95% CI 7·4—20·5). All regimens were well tolerated. Adverse events were reported by 599 patients, most commonly vomiting and dizziness. Other side-effects were less common and were not related to a specific treatment.

Interpretation

Artesunate—amodiaquine should not be used in Myanmar, because the other ACTs are substantially more effective. Artesunate—mefloquine provided the greatest post-treatment suppression of malaria. Adding a single dose of primaquine would substantially reduce transmission potential. Vivax malaria, not recurrent falciparum malaria, is the main complication after treatment of P falciparum infections in this region.
http://www.fightingmalaria.org/research.aspx?id=1509

MALARIA: Shortage of malaria drugs is largely artificial

Hamis Kaheru
21 Sep 2010
Findings by the Budget Monitoring Unit of the Ministry of Finance have revealed that the majority of people who go to government health centres for malaria drugs are not patients. They are mainly 'speculators' who keep the medicine in their homes for fear that they will fall sick when the medicine is no longer available at the health centre.
The study indicates that in Rukungiri District alone, only 4,000 out of 20,000 people per month who get free malaria drugs at public health centres are genuine patients. This means that Uganda loses 16,000 doses of anti-malarials every month per district. Consequently, many genuine patients will not get treatment and probably die of malaria - part of the 300 daily deaths. Understandably, health workers in rural health centres give out the medicine to everybody who asks for it because they lack facilities to carry out blood tests.
The study confirms what many in the health sector have heard before but probably could not figure out the magnitude of the problem. Ruhaama and other border areas such as Bukwo and Gulu also have other unique challenges. They have to attend to patients from neighbouring countries like Rwanda, Kenya and Sudan.

"We know that the medicines are meant for Ugandans but you cannot send away a patient because he is not Ugandan. That would be rude and unethical," a health worker in Ruhaama County, Ntungamo District, noted. Giving medicine to non-patients and non-citizens means that stocks meant to last two months are exhausted in a few days, leading to an outcry of shortages from those who seek treatment afterwards. Malaria is the most common disease in rural areas and Coartem is the recommended effective medicine.

The solution lies in compulsory screening of all those who claim to have malaria. Beginning next month, National Medical Stores (NMS) will start distributing Rapid Diagnostic Test (RDT) kits to every health centre alongside routine supplies. NMS intends to use part of the Shs90b from Global Fund to supply malaria RDTs free of charge. It is hoped that if those who feign sickness are cut out, almost every genuine patient might have access to free anti-malarial drugs.

Going by the study in Rukungiri, if 16,000 doses of Coartem are lost in every district per month, then about 1.6 million doses are lost countrywide every month. Then how many genuine malaria patients go to public health centres in the same period and fail to get Coartem? Are they more than 1.6m people? Whatever the numbers, it is clear that shortage of malaria drugs in the country is largely artificial and the RDTs should change this.

The kit is easy to use; it requires a simple prick on a finger for a blood sample to be dropped on the kit for it to show the appropriate colour that tells the status of the patient - the same way the pregnancy rapid test kits work. The RDTs should not only lead to shorter queues at public health centres but also enable the stocks to last longer, probably until the next delivery in two months time - thus significantly bringing down malaria deaths.

However, the public should also play their part in ensuring that the supplies denied to those who have been feigning sickness do not get out of the health centre to private clinics through other means.
http://www.fightingmalaria.org/news.aspx?id=1510

MALARIA: Antimalarial medicine diversion

Roger Bate, Kimberly Hess, Lorraine Mooney
September 2010
Antimalarial medicine diversion: stock-outs and other public health problems

Background:
Antimalarial medicine diversion has been seen across numerous African markets and can lead to serious stock-outs in the public sector, which can be dangerous to countries with high burdens of disease. This study discusses the numbers of diverted antimalarial medicines from several samplings in Africa.
Methods:
A total of 894 samples of antimalarial medicines were covertly purchased from private pharmacies in 11 African cities from late 2007 to early 2010. All medicine packages were visually inspected for correctness, in line with the protocol established by the Global Pharma Health Fund e.V. Minilab®, as well as for signs of diversion.
Results:
Overall, 6.5% (58 out of 894) of collected antimalarial medicines were found to be diverted, comprising 2.4% (5/210) of medicines collected in 2007 from six African cities, all of which were artemisinin-based combination therapies (ACTs); 2.3% (3/129) of medicines collected in 2008 in Lagos, Nigeria, two of which were ACTs; and 9% (50/555) of medicines collected in 2010 in 10 African cities, 35 of which were ACTs. ACT was by far the most diverted treatment in this study: 15.6% (5/32) of ACTs collected in 2007, and 30.7% (35/114) of ACTs collected in 2010.Conclusion: The number of diverted ACTs over the 33 months covered by this study is probably related to the laudable provision of vast amounts of donated or low-priced ACTs across African nations and the actual increase in diversion of these medicines into the private sector. The small sample sizes in this study might exaggerate any problem, but a potentially serious problem may well exist. To the extent that diversion of medicines exacerbates stock-outs, this is a public health problem, and a perversion of donor intent, but there are other possible harms of diversion, such as increased trade in counterfeit, and expired and otherwise substandard medicines.
http://www.dovepress.com/antimalarial-medicine-diversion-stock-outs-and-other-public-health-pro-peer-reviewed-article-RRTM

MALARIA: Some donated malaria drugs being stolen in Africa

Maria Cheng

01 Sep 2010

Millions of free malaria drugs are sent to Africa every year by international donors. New research is now providing evidence for what health workers have long suspected: some of the donated medication is being stolen and resold on commercial markets.During three periods from 2007 to 2010, American and British experts bought malaria medicines randomly from private pharmacies in 11 African cities. Of the 894 samples, they found 58, or 6.5 percent, were supposed to have been donated to government hospitals and clinics.The study will be published Thursday in the journal Research and Reports in Tropical Medicine and was paid for by the Legatum Institute, a U.S. philanthropic group with no ties to drug makers.The finding was particularly strong in artemesinin combination drugs, the best available malaria drugs, and those often purchased by international donors. In 2007, they found about 15 percent of such donated drugs had been stolen for resale. This year, it was nearly 30 percent.The authors acknowledge the sample sizes were small and could exaggerate the problem. Outside experts said donated drugs regularly disappear across corruption-plagued Africa and that the research was credible. There have been no large-scale published studies analyzing the problem."The study is important because it clearly documents something that we need to study (the issue) more closely," said Tido von Schoen-Angerer, a director at Medecins Sans Frontieres, which works across Africa.Von Schoen-Angerer said it is extremely difficult to determine the scale of the problem since drugs are not often followed from their origin to their ultimate destination in Africa.According to an audit last year by the U.S. President's Malaria Initiative, about $640,000 worth of medicines sent to Angola vanished from airports and the government's medicines warehouse."Critical malaria commodities are not reaching their intended beneficiaries and more Angolans may be unnecessary victims," the report said."We've heard about this kind of corruption anecdotally for years," said Julian Harris, a health expert at International Policy Network, a London-based think tank. He was not linked to the study. "But the response from funders has been to keep throwing millions of dollars' worth of these medicines into countries, even when there is evidence the drugs aren't reaching the needy."In the study, Roger Bate, a fellow at American Enterprise Institute in Washington DC, and colleagues focused on the most popular artemesinin combination malaria drug, Coartem, made by Novartis AG. They bought it in private markets in Ghana, Kenya, Tanzania, Uganda, Rwanda and Nigeria. Other drugs from Sanofi Aventis, Cipla and dozens of other companies were also included.Novartis makes two versions of the drug for Africa: the one to be donated comes in a flat white packet with a blister sheet of pills while the one for commercial markets is sold in an orange and white box.Bate, an economist who studies health policy, found donated drugs originally meant for Nigeria on sale in Kenya, drugs with "Not for Sale" stamped on them, and drugs packaged in the wrong local language, which suggests they were stolen from aid deliveries.Novartis declined to comment on the issue.The donated medicines were first bought by the Global Fund to fight AIDS, Tuberculosis and Malaria and the U.S. President's Malaria Initiative, a joint program led by the U.S. Agency for International Development and the U.S. Centers for Disease Control and Prevention. Both the Global Fund and the President's Malaria Initiative receive funds from international donors, including U.S. taxpayers.The Global Fund did not respond directly to questions about their drugs were being stolen. But in a recent review, the Fund discovered loopholes in its distribution system and admitted medicines could end up in commercial markets. It has previously suspended grants to Mauritania, Uganda and Zambia when it couldn't track where its money was going.Some experts dismissed the theft of donated drugs as a major health concern.Dr. David Sullivan, an associate professor in the Malaria Research Institute at Johns Hopkins Bloomberg School of Public Health, said he did not condone the theft of drugs, but thought the supply of high-quality drugs — like those bought by international donors — to private markets was actually a good thing.He said about half of Africans go to private health clinics, often flooded with cheap drugs that don't work. "The methods of getting better drugs is not ideal, but from a public health perspective, it's better that effective drugs are available in private clinics."But Henry Emboho Wanyama, a researcher in Uganda's malaria control department, said stolen drugs can have deadly consequences. "Drugs sent to health units are stolen by medical workers and the malaria patients who go there for treatment are told there are no drugs," he said."The patients who cannot afford (to buy) drugs ... end up dying."

http://www.google.com/hostednews/ap/article/ALeqM5jA8O8aJGbzRyY4x8UjWvfFtz7KSAD9HV3PB80

MALARIA: Uganda, Use of RDTs to improve malaria diagnosis and fever case management at primary health care facilities

Background
Early and accurate diagnosis of malaria followed by prompt treatment reduces the risk of severe disease in malaria endemic regions. Presumptive treatment of malaria is widely practised where microscopy or rapid diagnostic tests (RDTs) are not readily available. With the introduction of artemisinin-based combination therapy (ACT) for treatment of malaria in many low-resource settings, there is need to target treatment to patients with parasitologically confirmed malaria in order to improve quality of care, reduce over consumption of anti-malarials, reduce drug pressure and in turn delay development and spread of drug resistance. This study evaluated the effect of malaria RDTs on health workers' anti-malarial drug (AMD) prescriptions among outpatients at low level health care facilities (LLHCF) within different malaria epidemiological settings in Uganda.
Methods
All health workers (HWs) in 21 selected intervention (where RDTs were deployed) LLHF were invited for training on the use RDTs. All HWs were trained to use RDTs for parasitological diagnosis of all suspected malaria cases irrespective of age. Five LLHCFs with clinical diagnosis (CD only) were included for comparison. Subsequently AMD prescriptions were compared using both a 'pre - post' and 'intervention - control' analysis designs. In-depth interviews of the HWs were conducted to explore any factors that influence AMD prescription practices.
Results
A total of 166,131 out-patient attendances (OPD) were evaluated at 21 intervention LLHCFs. Overall use of RDTs resulted in a 38% point reduction in AMD prescriptions. There was a two-fold reduction (RR 0.62, 95% CI 0.55-0.70) in AMD prescription with the greatest reduction in the hypo-endemic setting (RR 0.46 95% CI 0.51-0.53) but no significant change in the urban setting (RR1.01, p-value = 0.820). Over 90% of all eligible OPD patients were offered a test. An average of 30% (range 25%-35%) of the RDT-negative fever patients received AMD prescriptions. When the test result was negative, children under five years of age were two to three times more likely (OR 2.6 p-value <0.001) to receive anti-malarial prescriptions relative to older age group. Of the 63 HWs interviewed 92% believed that a positive RDT result confirmed malaria, while only 49% believed that a negative RDT result excluded malaria infection.
Conclusion
Use of RDTs resulted in a 2-fold reduction in anti-malarial drug prescription at LLHCFs. The study demonstrated that RDT use is feasible at LLHCFs, and can lead to better targetting of malaria treatment. Nationwide deployment of RDTs in a systematic manner should be prioritised in order to improve fever case management. The process should include plans to educate HWs about the utility of RDTs in order to maximize acceptance and uptake of the diagnostic tools and thereby leading to the benefits of parasitological diagnosis of malaria.
http://www.malariajournal.com/content/9/1/200

MALARIA: advice to travellers

To watch children slip into the potentially fatal clutches of malaria is terrifying. It's the speed of the descent from good health to serious illness that is so frightening: at dawn they are fine, by dusk they could be in a coma, from which they might never wake. I know this because several years ago I was there – panic-stricken – watching my then eight-year old son, his mind drowning in delirium and his young body teetering on the brink of collapse.
He begged me to 'Just let me close my eyes for a bit, mum', and, desperate, I pleaded with him to stay awake. His decline took less than six hours. In the end he was fine – it meant an emergency airlift, an admission to hospital where he was administered artemisinin (a drug derived from the plant Artemesia annua) intravenously, and four long recuperative weeks out of school, but he did make a full recovery. We were lucky, luckier than the parents of the estimated 5,000 children that die from malaria every day.
Malaria is the world's biggest killer. It affects almost 500 million people a year and takes the lives of nearly 3 million – mostly in Africa, where a child is estimated to die from the disease every 30 seconds, at an estimated cost to the economy of more than £6bn a year.
Despite its much publicised Roll Back Malaria Partnership, the World Health Organisation has had limited success in 20 years. The only real impact the programme has had on the disease is through the introduction of insecticide-treated nets (ITNs), which are an effective prophylactic, particularly for children, when used correctly (but which remain heavily taxed in much of Africa).
Most of the world's millions of malaria sufferers are still not benefiting from life-saving drugs nearly five years after the WHO urged their widespread use. Since 2001, the UN health agency has recommended countries switch to artemisinin-based combination drugs (or ACTs) to treat malaria, which has become resistant to conventional medicines, like chloroquine.
The majority of sufferers understand very little about the disease or how it is transmitted (by the female mosquito, which must be pregnant, and which only bites between dusk and dawn).
Ronald Ross, a British doctor born in India, discovered it was the mosquito that transmitted malaria. Until then the popular theory was that foul-smelling gases emitted from swampy soils caused the disease – the word 'malaria' comes from the Italian, 'bad air'. The mortality rate at the time – over a million deaths a year – was reduced to less than 10,000 during the 1950s as a direct result of education and the eradication schemes initiated by Ross. Since the 60s, though, the disease has been on the increase – in 1960 only 10% of the world's population was at risk; that figure now stands at over 40%.
Today, as a result of poor vector control, global warming and intercontinental travel, malaria infects one in 10 of the world's population. It is present in over 100 countries (including eastern Europe, Russia and Turkey), visited by more than 125 million tourists every year, up to 30,000 of whom fall ill when they get home. Last year 1,754 Britons contracted malaria abroad – 1,300 of them the deadliest strain, Plasmodium falciparum (or cerebral malaria). Eleven of them died.
Poverty and poor education compound the problem of malaria in third-world countries, elevating mortality rates. Astonishingly, ignorance of the disease – despite the press coverage it receives and the access to world-class medicine – is a factor in first-world infection, too. Most British travellers who were infected with malaria last year admitted to failing to take correctly – or at all – oral malarial prophylaxis when visiting areas where the disease is endemic.
An investigation conducted earlier this year in the UK found that travellers who sought advice from alternative health centres (complaining that drugs prescribed by their GPs made them feel nauseous) were being offered 'dangerous' advice on malaria prevention and given unproven homoeopathic remedies. Conventional drugs prescribed by GPs are a combination of chloroquine and proguanil, mefloquine (Lariam), doxycycline and Malarone.
As a resident in Africa, I questioned my own doctor about the efficacy and side effects of these drugs. He dismissed chloroquine and proguanil as almost useless, since the parasite has been shown – in this region anyway – to have developed significant resistance to the combination. Lariam, he said, can cause serious neurological disturbances in as many as one in 10 people. Doxycycline increases photosensitivity, which means patients must be prepared to stay out of the sun. It can also interfere with the potency of oral contraception. Malarone, the most recent anti-malarial to be registered, is considered both effective and relatively easily tolerated, but expensive.
Without exception, all short-term visitors to a malarious area should seek advice from the experts (which include the London School of Hygiene and Tropical Medicine, the WHO and the Health Protection Agency) on malarial prophylaxis beforehand. The situation, however, is more complicated for expatriates living in endemic areas, partly because of the risk associated with long-term use of chemoprophylaxis and partly because there is limited data available on the sustained use of some drugs.
The Health Protection Agency suggests that 'the risk of serious side effects associated with long-term prophylactic use of chloroquine and proguanil is low. However, anyone who has taken chloroquine regularly for over five years and requires further prophylaxis should be screened twice-yearly for early retinal changes'. Even before these changes become apparent, there could be other intolerable side effects: my husband, for example, is unable to take proguanil (Paludrine) as it gives him appallingly bad mouth ulcers, which render him unable to eat.
Research suggests there is no increased risk of serious side effects with long-term use of mefloquine (Larium), assuming a person can tolerate it in the short term. Experience of doxycycline in long-term use is limited, though the available data is reassuring (however, like mefloquine, it must be avoided during pregnancy). In many parts of the world, oral prophylaxis is not a guaranteed form of protection; Plasmodium falciparum is increasingly resistant to various antimalarial drugs (indeed my son was on a chloraquine/proguanil combination when he contracted this particularly virulent strain of the disease). As the WHO warns, no antimalarial prophylactic regimen gives complete protection.
Those travelling to malarious areas for extended periods of time (over six months) – or living there (particularly in the case of women, who may become pregnant, and young children) – need to balance the risk of infection against the benefits and side effects of oral prophylaxis; sometimes taking a pill daily gives a false sense of security and might result in laziness when it comes to other prophylactic measures – sleeping under nets, for example, spraying rooms or burning mosquito coils at night.
The basics
Expatriates, 30% of whom develop malaria within two years, need to be vigilant about not being bitten, rather than relying on chemoprophylaxis alone, as chemoprophylaxis has been shown to be insufficient protection. Prevailing guidelines, as laid out by the WHO and HPA, promote four (ABCD) principles of malaria protection:
• Be aware of the risk, the incubation period (from seven days up to several months) and the main symptoms: flu-like to begin with, chills, headache . Sometimes a cough develops.
• Avoid being bitten by mosquitoes, especially between dusk and dawn – apply mosquito repellent to the skin, wear long sleeves, trousers, socks and shoes, sleep under a light in a room where a coil is being burned. Sleeping under a fan or in an air-conditioned room can also help, as can fixing mosquito mesh to windows.
• Take antimalarial drugs (chemoprophylaxis), as advised by a doctor, to prevent infection from developing into clinical disease.
• Immediately seek diagnosis and treatment if a fever develops one week or more after entering an area where there is a risk of malaria, and up to three months (and even longer) after departure from a risk area. Early diagnosis and treatment can be life-saving; Plasmodium falciparum can be fatal within 24 hours. A blood sample should be examined for malaria parasites. If no parasites are found in the first slide yet clinical suspicion of malaria remains, a series of blood samples should be taken at six- to 12-hour intervals and examined vigilantly. Sometimes taking a chemoprophylaxis can mask results, so this should always be mentioned to an examining doctor. In the end, as my doctor here observes, the only sure-fire way to avoid infection in a malarial area is to avoid being bitten.
http://www.guardian.co.uk/money/2008/mar/19/expat-finance-malaria-prevention

MALARIA: personal experience and review

To watch children slip into the potentially fatal clutches of malaria is terrifying. It's the speed of the descent from good health to serious illness that is so frightening: at dawn they are fine, by dusk they could be in a coma, from which they might never wake. I know this because several years ago I was there – panic-stricken – watching my then eight-year old son, his mind drowning in delirium and his young body teetering on the brink of collapse.
He begged me to 'Just let me close my eyes for a bit, mum', and, desperate, I pleaded with him to stay awake. His decline took less than six hours. In the end he was fine – it meant an emergency airlift, an admission to hospital where he was administered artemisinin (a drug derived from the plant Artemesia annua) intravenously, and four long recuperative weeks out of school, but he did make a full recovery. We were lucky, luckier than the parents of the estimated 5,000 children that die from malaria every day.
Malaria is the world's biggest killer. It affects almost 500 million people a year and takes the lives of nearly 3 million – mostly in Africa, where a child is estimated to die from the disease every 30 seconds, at an estimated cost to the economy of more than £6bn a year.
Despite its much publicised Roll Back Malaria Partnership, the World Health Organisation has had limited success in 20 years. The only real impact the programme has had on the disease is through the introduction of insecticide-treated nets (ITNs), which are an effective prophylactic, particularly for children, when used correctly (but which remain heavily taxed in much of Africa).
Most of the world's millions of malaria sufferers are still not benefiting from life-saving drugs nearly five years after the WHO urged their widespread use. Since 2001, the UN health agency has recommended countries switch to artemisinin-based combination drugs (or ACTs) to treat malaria, which has become resistant to conventional medicines, like chloroquine.
The majority of sufferers understand very little about the disease or how it is transmitted (by the female mosquito, which must be pregnant, and which only bites between dusk and dawn).
Ronald Ross, a British doctor born in India, discovered it was the mosquito that transmitted malaria. Until then the popular theory was that foul-smelling gases emitted from swampy soils caused the disease – the word 'malaria' comes from the Italian, 'bad air'. The mortality rate at the time – over a million deaths a year – was reduced to less than 10,000 during the 1950s as a direct result of education and the eradication schemes initiated by Ross. Since the 60s, though, the disease has been on the increase – in 1960 only 10% of the world's population was at risk; that figure now stands at over 40%.
Today, as a result of poor vector control, global warming and intercontinental travel, malaria infects one in 10 of the world's population. It is present in over 100 countries (including eastern Europe, Russia and Turkey), visited by more than 125 million tourists every year, up to 30,000 of whom fall ill when they get home. Last year 1,754 Britons contracted malaria abroad – 1,300 of them the deadliest strain, Plasmodium falciparum (or cerebral malaria). Eleven of them died.
Poverty and poor education compound the problem of malaria in third-world countries, elevating mortality rates. Astonishingly, ignorance of the disease – despite the press coverage it receives and the access to world-class medicine – is a factor in first-world infection, too. Most British travellers who were infected with malaria last year admitted to failing to take correctly – or at all – oral malarial prophylaxis when visiting areas where the disease is endemic.
An investigation conducted earlier this year in the UK found that travellers who sought advice from alternative health centres (complaining that drugs prescribed by their GPs made them feel nauseous) were being offered 'dangerous' advice on malaria prevention and given unproven homoeopathic remedies. Conventional drugs prescribed by GPs are a combination of chloroquine and proguanil, mefloquine (Lariam), doxycycline and Malarone.
As a resident in Africa, I questioned my own doctor about the efficacy and side effects of these drugs. He dismissed chloroquine and proguanil as almost useless, since the parasite has been shown – in this region anyway – to have developed significant resistance to the combination. Lariam, he said, can cause serious neurological disturbances in as many as one in 10 people. Doxycycline increases photosensitivity, which means patients must be prepared to stay out of the sun. It can also interfere with the potency of oral contraception. Malarone, the most recent anti-malarial to be registered, is considered both effective and relatively easily tolerated, but expensive.
Without exception, all short-term visitors to a malarious area should seek advice from the experts (which include the London School of Hygiene and Tropical Medicine, the WHO and the Health Protection Agency) on malarial prophylaxis beforehand. The situation, however, is more complicated for expatriates living in endemic areas, partly because of the risk associated with long-term use of chemoprophylaxis and partly because there is limited data available on the sustained use of some drugs.
The Health Protection Agency suggests that 'the risk of serious side effects associated with long-term prophylactic use of chloroquine and proguanil is low. However, anyone who has taken chloroquine regularly for over five years and requires further prophylaxis should be screened twice-yearly for early retinal changes'. Even before these changes become apparent, there could be other intolerable side effects: my husband, for example, is unable to take proguanil (Paludrine) as it gives him appallingly bad mouth ulcers, which render him unable to eat.
Research suggests there is no increased risk of serious side effects with long-term use of mefloquine (Larium), assuming a person can tolerate it in the short term. Experience of doxycycline in long-term use is limited, though the available data is reassuring (however, like mefloquine, it must be avoided during pregnancy). In many parts of the world, oral prophylaxis is not a guaranteed form of protection; Plasmodium falciparum is increasingly resistant to various antimalarial drugs (indeed my son was on a chloraquine/proguanil combination when he contracted this particularly virulent strain of the disease). As the WHO warns, no antimalarial prophylactic regimen gives complete protection.
Those travelling to malarious areas for extended periods of time (over six months) – or living there (particularly in the case of women, who may become pregnant, and young children) – need to balance the risk of infection against the benefits and side effects of oral prophylaxis; sometimes taking a pill daily gives a false sense of security and might result in laziness when it comes to other prophylactic measures – sleeping under nets, for example, spraying rooms or burning mosquito coils at night.
http://www.guardian.co.uk/money/2008/mar/19/expat-finance-malaria-prevention

MALARIA: Fish nets join mosquito nets against malaria

JOHANNESBURG, 2 July 2010 (IRIN) - New drugs to fight malaria may well lie at the bottom of the ocean, according to researchers studying over 2,500 samples from marine organisms collected at depths of over 900 metres. They have already found 300 that contain substances that can kill the parasite. "Healing powers for one of the world's deadliest diseases may lie within sponges, sea worms and other underwater creatures," said an internal publication by the University of Central Florida (UCF) after a study of samples collected off the Florida coast in the United States with the help of the Harbor Branch Oceanographic Institute in Fort Pierce, Florida. "So far we have a hit rate of over 10 percent," said Debopam Chakrabarti, Professor of Molecular Biology and Microbiology at UCF, who is leading the research. He was "quite enthused by the promise of the project", but warned that "early promise does not always materialize" into a usable drug. Chakrabarti has spent over 20 years researching treatments for the mosquito-borne illness, and turned to the largely unexplored biological potential of the ocean because "[current] drugs are becoming increasingly less effective and [malaria] is still killing," he told IRIN. The UN World Health Organization has noted that about 3.3 billion people - half of the world's population - are at risk of malaria, and around 1 million people worldwide are killed by it every year.

MALARIA: substandard medication

Background
Two major cities in West Africa, Accra, the capital of Ghana, and Lagos, the largest city of Nigeria, have significant problems with substandard pharmaceuticals. Both have actively combated the problem in recent years, particularly by screening products on the market using the Global Pharma Health Fund e.V. Minilab protocol. Random sampling of medicines from the two cities at least twice over the past 30 months allows a tentative assessment of whether improvements in drug quality have occurred. Since intelligence provided by investigators indicates that some counterfeit producers may be adapting products to pass Minilab tests, the results are compared with those from a Raman spectrometer and discrepancies are discussed.
Methods
Between mid-2007 and early-2010, samples of anti-malarial drugs were bought covertly from pharmacies in Lagos on three different occasions (October 2007, December 2008, February 2010), and from pharmacies in Accra on two different occasions (October 2007, February 2010). All samples were tested using the Minilab protocol, which includes disintegration and active ingredient assays as well as visual inspection, and most samples were also tested by Raman spectrometry.
Results
In Lagos, the failure rate in the 2010 sampling fell to 29% of the 2007 finding using the Minilab protocol, 53% using Raman spectrometry, and 46% using visual inspection. In Accra, the failure rate in the 2010 sampling fell to 54% of the 2007 finding using the Minilab protocol, 72% using Raman spectrometry, and 90% using visual inspection.
Conclusions
The evidence presented shows that drug quality is probably improving in both cities, especially Lagos, since major reductions of failure rates over time occur with all means of assessment. Many more samples failed when examined by Raman spectrometry than by Minilab protocol. The discrepancy is most likely caused by the two techniques measuring different aspects of the medication and hence the discrepancy may be the natural variation in these techniques. But other explanations are possible and are discussed.
http://www.malariajournal.com/content/9/1/157

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: demand for microscopes

THE lack of microscopes in government-aided health centres in Bushenyi district has hindered the fight against malaria, the district medical officer, Dr. Celestine Barigye, has said. Barigye said because of the shortage of microscopes, medical officers cannot diagnose diseases thoroughly. Barigye said when the patients go to health centres complaining of fever, the medical workers just prescribe malaria medicine even when they (patients) are not suffering from the disease. Barigye was speaking at a one-day malaria control workshop for stakeholders at Katungu Mothers’ Union Conference Centre in Bushenyi town. The workshop was organised by the West Ankole Diocese. Barigye called upon the Government to intensify the distribution of insecticide-treated mosquito nets, especially to the rural people who cannot afford them. He said to have a malaria-free country, there was need to sensitise the population about the disease. The diocese’s planning and development officer, Richard Mwesigwa, said the Church of Uganda had partnered with the district to distribute mosquito nets to vulnerable people.
http://www.newvision.co.ug/D/8/18/722638

MALARIA: Progress and challenges to control malaria in a remote area of Chittagong hill tracts, Bangladesh

Background
Malaria is endemic in 13 eastern districts where the overall infection prevalence is 3.97%. In 2006, Bangladesh received US$ 36.9 million from the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) to support the national malaria control programme of Bangladesh. Objectives The objective of this study was to i) clarify factors associated with treatment-seeking behaviours two years after implementation of national malaria control programme, ii) investigate the distribution of LLIN and iii) re-treatment of ITN in remote areas of a CHT district of Bangladesh.
Methods
All households of Rajasthali sub-district of Rangamati district (households about 5,322, population about 24,097), all BRAC health workers (n = 15), health facilities and drug vendors' locations were mapped. Distances from households to health facilities, BRAC health workers and drug vendors were calculated. Logistic regression analysis was performed to assess the associations between the choice of the treatment and the distance to various treatment sources, education, occupation and ethnicity. SaTScan was used to detect clustering of treatment-seeking approaches.
Findings
LLIN distribution and the re-treatment of ITN exceeded target goals. The most common treatment facility for malaria-associated fever was malaria control programme led by BRAC and government (66.6%) followed by the drug vendor (48.8%).
Conclusion
Closeness to health facilities runs by the malaria control programme and drug vendors were significantly associated with the choice of treatment. A high proportion of people preferred drug vendors without having a proper diagnosis. Drug vendors are highly patronized and thus there may be an opportunity to improve and integrate their services in public health programmes. Otherwise this may cause incomplete treatment, misuse of anti-malarial drugs, contribute to the risk of drug resistance and jeopardize the present malaria control efforts in Bangladesh.
Malaria Journal 2010, 9:156 (10 June 2010)

MALARIA: Drug developed to prevent parasite entry into red cell

CANBERRA, June 3 (Xinhua) -- Australian scientists on Thursday said they have found a unique way to block a malaria infection, opening up a new front in the war on the mosquito-borne parasite which infects 400 million people every year, Australian Associated Press reported on Thursday.
Researchers at the Melbourne-based Walter and Eliza Hall Institute for Medical Research have identified an alternative method to that used by conventional treatments, which kills off the parasite once it has gained access to a person's red blood cells.
The institute's Dr James Beeson said the new method had proven capable of stopping the parasite from entering the cells altogether, robbing it of the safe haven it needed to multiply while hiding from the body's defenses.
"All of the currently licensed anti-malarial drugs that are used in humans act by inhibiting or slowing down the development of the parasite once it is inside the red blood cell," Beeson said.
"This (alternative) approach is to block the parasite from getting inside the red blood cell in the first place ... it would be ideal to use this approach in combination with an existing anti- malarial so it would be a two-pronged attack.
"One would try to stop the parasite from getting in and the other would be trying to stop the development of any parasite within the red blood cells."
The scientists found the blood-thinning drug heparin, which is used to treat blood clots, was effective at stopping the malaria parasite, most commonly Plasmodium falciparum, from attaching and burrowing into red blood cells.
They then developed similar molecules that boosted this effect against the parasite but had no blood-thinning effect.
Beeson said trials to ensure its safety, reformulated and "two- pronged" anti-malarial treatments could be introduced to the world in five to 10 years.
It would boost the protection for travelers in malaria-prone developing nations and provide a more effective treatment for malaria once infection took hold, resulting in less sickness and fewer deaths.
About one million people, mostly children, die as a result of malaria every year.
http://news.xinhuanet.com/english2010/health/2010-06/03/c_13331265.htm

MALARIA: Poverty is barrier to access to treatment

Prompt access to effective malaria treatment is central to the success of malaria control worldwide, but few fevers are treated with effective anti-malarials within 24 hours of symptoms onset. The last two decades saw an upsurge of initiatives to improve access to effective malaria treatment in many parts of sub-Saharan Africa. Evidence suggests that the poorest populations remain least likely to seek prompt and effective treatment, but the factors that prevent them from accessing interventions are not well understood. With plans under way to subsidize ACT heavily in Kenya and other parts of Africa, there is urgent need to identify policy actions to promote access among the poor. This paper explores access barriers to effective malaria treatment among the poorest population in four malaria endemic districts in Kenya.
Methods
The study was conducted in the poorest areas of four malaria endemic districts in Kenya. Multiple data collection methods were applied including: a cross-sectional survey (n=708 households); 24 focus group discussions; semi-structured interviews with health workers (n=34); and patient exit interviews (n= 359).
Results
Multiple factors related to affordability, acceptability and availability interact to influence access to prompt and effective treatment. Regarding affordability, about 40 percent of individuals who self-treated using shop-bought drugs and 42 percent who visited a formal health facility reported not having enough money to pay for treatment, and having to adopt coping strategies including borrowing money and getting treatment on credit in order to access care. Other factors influencing affordability were seasonality of illness and income sources, transport costs, and unofficial payments. Regarding acceptability, the major interrelated factors identified were provider patient relationship, patient expectations, beliefs on illness causation, perceived effectiveness of treatment, distrust in the quality of care and poor adherence to treatment regimes. Availability barriers identified were related to facility opening hours, organization of health care services, drug and staff shortages.
Conclusions
Ensuring that all individuals suffering from malaria have prompt access to effective treatment remains a challenge for resource constrained health systems. Policy actions to address the multiple barriers of access should be designed around access dimensions, and should include broad interventions to revitalize the public health care system. Unless additional efforts are directed towards addressing access barriers among the poor and vulnerable, malaria will remain a major cause of morbidity and mortality in sub-Saharan Africa.
http://www.malariajournal.com/content/9/1/144

MALARIA: Clinton Foundation

Malaria is the single greatest killer of African children, claiming the lives of roughly 1 million young children every year and hindering the development of many who survive. Despite a surge in funding and attention from the global community in recent years, the majority of African families are not benefitting from the tools necessary to stop malaria, such as bed nets and effective medicines, because of a lack of access or efficient use. Building on CHAI's approach in successfully changing the marketplace for HIV/AIDS medicines, we expanded our efforts in 2007 to increase access to effective malaria treatment.
CHAI's Approach
Unlike some diseases, malaria can be cured quickly and fully with over-the-counter medicine and without a doctor's visit. Over the last 20 years, however, the malaria parasite has grown resistant to many of the leading treatments sold at local drug shops. Effective alternatives, known as artemisinin-based combination therapies (ACTs), are now available as an alternative to the ineffective medicine, but remain too expensive for many patients to afford, costing $10 - for one treatment of medicine that can treat the disease - in communities where most people make less than $2 per day.
Malaria experts theorized that subsidizing the cost of malaria medications to private wholesalers would have a dramatic effect on the price of ACTs. In 2007, CHAI decided to pilot this theory by buying ACTs from the manufacturer and selling them at a 95 percent reduced price. Within the first six months of the pilot, the price decreased to 50 cents, and ACT uptake increased by 45 percent. The results of this pilot now are helping to guide the design of a potential global subsidy for ACTs, known as the Affordable Medicines Facility for Malaria (AMFm).
Additionally, CHAI has worked with six suppliers to make ACTs more affordable in developing countries around the world. On July 17, 2008, President Clinton announced an agreement with these suppliers that lowered the price of one leading malaria medicine by 30 percent, and reduced the price volatility of artmesinin, a key raw ingredient used to make ACTs, by 70 percent. Over the past six years alone, the price of this key raw material has ranged from $150 to $1,100, a 700 percent swing in pricing. This agreement enables affordable access to the highest quality medicines for hundreds of thousands of people across the more than 70 countries in CHAI's Procurement Consortium.
http://www.clintonfoundation.org/what-we-do/clinton-health-access-initiative/our-approach

MALARIA: fake medication

May 14 (Bloomberg) -- At 12:30 p.m. on May 6, Ampem Dankwah sends a cell-phone message from the lobby of a downtown cafe in Accra, Ghana: “GH4F9H84B4.” His text opens a front in the war on sham malaria drugs.
Within 1.2 seconds, Dankwah’s transmission is routed to a Hewlett-Packard Co. data center in Galway, Ireland, where a computer verifies the code and responds, “OK.” It is the first test of a system developed by HP and Dankwah’s employer, mPedigree Network Ltd., to help millions of Africans avoid counterfeit malaria pills with little or no active medicine, Bloomberg Businessweek reports in its May 17 issue.
Under the plan, legitimate drugs will come with a scratch- off panel hiding 10 digits. Consumers will send the code to a widely advertised number, and receive a reply confirming or disputing the product’s authenticity. The system is designed to detect fakes that in some African nations make up half the drugs sold for malaria, a mosquito-borne disease that is the single greatest killer of African children, according to the William J. Clinton Foundation in New York.
“A big advantage of it is that it empowers the consumer,” said Paul Newton, a Vientiane, Laos-based researcher from the U.K.’s University of Oxford who studies counterfeit drugs. Pharmaceutical makers may welcome the development “because it would increase public confidence in medicines,” Newton said in a telephone interview.
http://www.bloomberg.com/apps/news?pid=20601085&sid=a0_anlNoJCgU

MALARIA: Computer control of drug inventory

Malaria has been in the category of Aids and tuberculosis — as killer diseases — and deserves deathblow at whatever cost.
However, studies show the fight against the killer disease has been jeorpadised not by lack of enough drugs, but poor distribution. Many patients die due to poor treatment and shortage of drugs at health centres where they are needed most yet, in others, the drugs lie unused in stores.
A new technology that uses SMS to track movement of drugs and stock levels in health centres is boosting the war against malaria, which claims more than 880,000 lives a year in Africa.
The technology has successfully been piloted in Tanzania and promises the disease can be controlled by prompt distribution of drugs.
A multinational computer, technology and IT consulting company, IBM, in partnership with Novartis and Vodafone, together with Roll Back Malaria and Tanzania’s Ministry of Health and Social Welfare have reaped from the technology dubbed ‘SMS for Life’. The system tracks movement and the supply of anti-malaria drugs in sub-Saharan Africa.
‘SMS for Life’ pilot project in Tanzania used mobile and electronic mapping technology to track and manage delivery and stock levels of the drugs to health facilities in rural areas.
Avoid stock-outs
Accurately monitoring the amount of medication available in a given location reduces the risk of running out of stock and ensures treatments are available to patients, even in the most remote areas, where and when they are needed. Common anti-malarial drugs include artemisinin-based combination therapies (ACTs) and quinine injectables.
"Use of mobile phones to keep everyone informed of the stock position of anti-malaria medicines has prompted the supply chain to replenish stocks on time to avoid stock-outs," says David Mwakyusa, Tanzania’s Health and Social Welfare Minister.
"We have saved hundreds of lives in the districts we piloted the programme," adds Prof Mwakyusa.
‘SMS for Life’ sends weekly automated alerts to staff at participating healthcare facilities, prompting them to check the stock and reply using an SMS with stock details.
These messages are collected in a central web-based system that provides information to district medical officers and other users. The data is accessible via the Internet or mobile phones.
The information allows the officers to re-distribute treatments to needy areas and coordinate emergency deliveries to health facilities as necessary.
Studies indicate that millions of people die of malaria in Africa due to delayed administration of drugs.
The project managers say many lives can now be saved in malaria-prone countries, including Kenya, if authorities adopt the technology.
At the start of the piloting in Tanzania, 25 per cent of health facilities did not have any ACTs in stock, but by the end, 95 per cent had at least one dosage form.
Using ‘SMS for Life’, participating health centres increased availability of malaria treatments threefold.
Prof Awa Marie Coll-Seck, executive director of the Roll Back Malaria Partnership and Chair of the ‘SMS for Life’ Steering Committee in Lindi Rural says stock-outs were completely eliminated in all 48 facilities by week eight of the pilot.
Rewarding efforts
"The pilot has demonstrated that finally we have a solution to the longstanding problem of stock-outs at the health facility level," adds Jim Barrington, ‘SMS for Life’ Programme Director and former Chief Information Officer at Novartis.
"It is rewarding to see how a unique partnership and the innovative use of everyday technologies can positively impact the lives of malaria patients and families," he adds. "Malaria is a preventable disease, but without appropriate treatment it is life threatening."
"I look forward to a time when all clinics will use the system," says Joaquim Croca, Head of Health at Vodafone Group.
And Peter Ward of IBM, who is also the ‘SMS for Life’ Project Manager says, "This is an example of a truly innovative solution helping to solve a humanitarian problem."
In Kenya, cases of drug shortage in hospitals when stocks rot at the national store have been rampant.
Thus the SMS technology will definitely boost the war against malaria by ensuring quick stocking of dugs as need arises.
http://www.standardmedia.co.ke/InsidePage.php?id=2000009114&cid=4&ttl=Fighting%20malaria%20via%20the%20SMS