MALARIA: 'Needle-Free' Intervention as Natural Vaccine Against Malaria

July 23, 2010 — A study published in the journal Science Translation Medicine proposes that preventative treatment with affordable and safe antibiotics in people living in areas with intense malaria transmission has the potential to act as a 'needle-free' natural vaccine against malaria and may likely provide an additional valuable tool for controlling and/or eliminating malaria in resource-poor settings.
The research, conducted by a multinational team of researchers from the London School of Tropical Medicine and Hygiene (LSHTM), Heidelberg University School of Medicine, the Max Planck Institute for Infection Biology, Germany, and the KEMRI-Wellcome Trust Research Programme, Kenya, found that infection with malaria parasites during administration of preventative antibiotics developed a vaccine-like immunity against re-infection.
Approximately half the world's population is at risk of malaria and about one million people (mainly children living in sub-Saharan Africa) die each year from malaria, a mosquito-borne parasitic disease. Malaria parasites are transmitted to people through the bite of an infected Anopheles mosquito. Only an estimated 10 to 100 parasites per mosquito bite invade the liver where they replicate. About a week after infection, tens of thousands of parasites are released into the bloodstream where they are responsible for malaria's recurring fevers and cause life-threatening complications.
In this study, the researchers showed that the antibiotics caused a cellular defect in malaria parasites during their passage into the liver of the infected host. This action did not prevent parasite replication in the liver but blocked the malaria parasite's fatal conversion to the disease causing blood stage. The very late arrest of parasites in the liver allowed the immune system to mount a robust defence against subsequent infections, akin to experimental whole organism vaccine strategies using attenuated parasites.
As already established, antibiotics, especially in combination with other anti-malarial drugs, are safe and affordable drugs against an acute malaria infection. The novel concept is to take advantage of the immunological benefit of antibiotic prophylaxis in areas of moderate to high malaria transmission. In these settings, humans are continuously exposed to new malaria infections delivered by natural mosquito transmission that can be prevented by antibiotics. In the liver, a surplus of parasites presented to the immune system results in robust induction of memory immune responses that can recognize and destroy future malaria infections in the liver, when antibiotics are no longer taken.
Dr Steffen Borrman co-author on the paper says that 'this proof-of-principle study attempts to bridge a gap between basic malaria research and a rapid translation to a potential application in malaria-endemic countries. An important follow-up of this work is the validation of our experimental approach by clinical trials in humans. If successful, periodic administration of antibiotics, preferably in drug combinations, in high-risk population groups, particularly young, non-immune children, may provide an additional valuable tool for controlling and/or eliminating malaria in resource-poor settings.'
http://www.sciencedaily.com/releases/2010/07/100723112711.htm

TUBERCULOSIS: South African mining risks

Dust-choked mine shafts, crowded working conditions and stifling hostels where up to 16 miners share a room — all conspire to make mining a more important contributor to tuberculosis in Africa than had been realized, a new study finds.
Rates of the illness have doubled in Africa over the past two decades, and have tripled in South Africa, which even in 1996 had the highest TB rates in the world. Until now it has been assumed that the increases were driven by Africa’s high rates of infection with the AIDS virus, which weakens the immune system, helping latent TB become active.
But researchers from Brown and Oxford Universities, the London School of Hygiene and Tropical Medicine, and the University of California, San Francisco, compared 44 African countries and found that even some with low rates of H.I.V. infection rates had high TB rates. When a country’s mines shut down, tuberculosis often fell. The study appeared in The American Journal of Public Health.
The paper notes that many miners are migrant laborers who may go home only once or twice a year. Not only can they infect their wives and children, the authors found, but they stop seeing the mine clinic doctors who are familiar with tuberculosis and may interrupt taking their antibiotics, increasing the chances that they will develop a drug-resistant strain.
Gold seems to be the most dangerous product to mine, because workers in those deep, hot shafts breathe in more rock dust.
http://www.nytimes.com/2010/06/22/health/22glob.html?_r=1

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?

Malaria in pregnancy: preventive medication

Pfizer and the Medicines for Malaria Venture have agreed to co-develop a fixed-dose combination therapy of azithromycin dihydrate (AZ) and chloroquine phosphate (CA) for the intermittent preventive treatment of Plasmodium falciparum malaria in pregnacy (IPTp). Phase III trials are expected to start in Africa later this year and include up to 5,000 participants.
The agreement between Pfizer and MMV builds on two years of informal collaborative research by the organizations together with the London School of Hygiene and Tropical Medicine (LSHTM).
Under the terms of the formal deal, Pfizer will seek marketing approval for the drug combination in selected malaria-endemic African countries and will work with the MMV to introduce the therapy in relevant territories. MMV will also provide support and advocacy on several levels including the development of a patient education campaign and recommendations on strategies for registration in malaria-endemic countries. The LSHTM will coordinate clinical trials of the AZ-CQ combination.
Pfizer says that WHO figures estimate some 30 million pregnant women in malaria-endemic African regions are at risk of the disease every year. “Pfizer believes that an affordable price for public sector sales of the medicine in endemic countries, if approved, is an important step towards increasing access and safe intermittent preventive treatment for pregnant women,” remarks Jean-Michel Halfon, president and GM of Pfizer’s emerging markets business.
http://www.genengnews.com/news/bnitem.aspx?name=80849261

Chlorfenapyr insecticide

BASF has signed an agreement with the London School of Hygiene & Tropical Medicine (LSHTM) and the Innovative Vector Control Consortium (IVCC) to develop a new generation of malaria prevention products based on the BASF insecticide chlorfenapyr. These products, the first of which is expected to be available next year, will help reduce malaria in areas where mosquitoes are already becoming resistant to existing solutions. The products will include residual wall sprays as well as long-lasting insecticide treated nets (LLIN). LLIN are pointed out as one of the most efficient method to prevent malaria. The net creates the physical barrier that prevents mosquitoes from reaching individuals and the impregnated insecticide guarantees that once the mosquito has contact with the net, it will get knocked-down.
http://www.agro.basf.com/agr/AP-InternetPreview/en_GB/content/news_room/news/next-generation-malaria-control