MMV and partners have completed the first-ever comparative analysis of all currently available and in-development antimalarials in terms of the steps they target in the parasite’s lifecycle. This information provides the missing pieces of the puzzle needed to develop future medicines able to block transmission of the parasite from person to person.

Current medicines mostly target the malaria parasite at the blood stage in its lifecycle because this is the step that leads to clinical symptoms. To be able to block transmission of the parasite, however, we need to be able to kill the parasite at multiple points in its lifecycle, namely the sexual and vector (mosquito) stages.

The research teams from Imperial College London, Genomics Institute of the Novartis Research Foundation, Swiss TPH, University of Basel, Scripps Research Institute and Medicines for Malaria Venture were able to reproduce the complex biology of the malaria parasite throughout its lifecycle, in the laboratory. This then allowed them to test the activity of 50 anti-infective molecules (the vast majority being available and in-development antimalarials) against each ‘laboratory-produced step’ to determine exactly where they act.

The research revealed a number of interesting findings. Specifically, some already available antimalarials, such as pyronaridine and atovaquone, can target the liver and sexual stages of the parasite in addition to the blood stage. The endoperoxide OZ439, currently in Phase II clinical trials, and a new 8-aminoquinoline, NPC-1161B, also demonstrated transmission-blocking potential.

“These specific findings will be critical in guiding the selection and combination of next-generation molecules to succeed artemisinin combination therapy and will support the drive to eradicate malaria,” said Tim Wells, CSO of MMV, “while the complete data provides us with a benchmark against which to assess any newly discovered molecules.”

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One hundred million treatments of Coartem® Dispersible (artemether-lumefantrine), an antimalarial developed especially for children with Plasmodium falciparum malaria, have been delivered by Novartis to 39 malaria-endemic countries, Medicines for Malaria Venture (MMV) announced today.

Coartem® Dispersible is the product of the partnership between MMV and Novartis. It is the first WHO prequalified child-friendly artemisinin-combination therapy (ACT) and addresses an unmet need for paediatric medicines. Young children in Africa are disproportionately affected by malaria, with 86% of malaria deaths occurring in children under the age of 5 years.

Ahead of the international community’s call for better child-friendly medicines, MMV and Novartis signed an agreement in 2003 to develop the first paediatric ACT. The child-friendly formulation was launched in 2009.

“This is indeed a landmark achievement for both Novartis and MMV,” said MMV’s CEO, David Reddy. “Never before have 100 million paediatric treatments been distributed in such a short time frame to assist children suffering from malaria. Today, we have proved that partnerships can succeed in not only developing new, high-quality medicines for malaria but also delivering these to vulnerable populations. This success only increases our determination to address remaining unmet medical needs by bringing forward new antimalarial medicines as our part in defeating this disease. We are indebted to our partners like Novartis and to our donors*, who are crucial to the success of MMV.”

“Reaching the 100 million milestone in less than 3 years is the culmination of a successful collaboration between Novartis and MMV,” said Linus Igwemezie, Head of the Novartis Malaria Initiative. “Partnerships are at the core of the Novartis Malaria Initiative and we are delighted at the success these collaborations have had in providing effective malaria treatments to millions of patients who are most in need. There is still much to be done and we are committed to continue applying our innovation power to help improve access to affordable and quality antimalarials.”

“The success of Coartem® Dispersible shows why research and development is at the heart of the British Government’s fight against malaria,” said Stephen O’Brien, Under-Secretary of State for International Development, UK. “Product Development Partnerships, such as Medicines for Malaria Venture, bring together the public and private sectors to use their combined expertise to develop new drugs. Children are the most vulnerable to this deadly disease. By developing this paediatric treatment, Medicines for Malaria Venture and Novartis have given the hope of a healthier life to millions of the world’s poorest children.”

Focused measures have been taken to facilitate the uptake of this medicine, including registration in 39 malaria-endemic countries, a without-profit pricing model and special packaging designed to improve compliance. These measures have not only led to increased demand but also to an accelerated uptake, underlining the advantage of the paediatric formulation. By reaching this milestone the Novartis Malaria Initiative and MMV have proven that drug development partnerships can truly advance the fight against malaria.

Background

Human African trypanosomiasis (HAT) or sleeping sickness leads to a complex neuropsychiatric syndrome with characteristic sleep alterations. Current division into a first, hemolymphatic stage and second, meningoencephalitic stage is primarily based on the detection of white blood cells and/or trypanosomes in the cerebrospinal fluid. The validity of this criterion is, however, debated, and novel laboratory biomarkers are under study. Objective clinical HAT evaluation and monitoring is therefore needed. Polysomnography has effectively documented sleep-wake disturbances during HAT, but could be difficult to apply as routine technology in field work. The non-invasive, cost-effective technique of actigraphy has been widely validated as a tool for the ambulatory evaluation of sleep disturbances. In this pilot study, actigraphy was applied to the clinical assessment of HAT patients.

Methods/Principal Findings

Actigraphy was recorded in patients infected by Trypanosoma brucei gambiense, and age- and sex-matched control subjects. Simultaneous nocturnal polysomnography was also performed in the patients. Nine patients, including one child, were analyzed at admission and two of them also during specific treatment. Parameters, analyzed with user-friendly software, included sleep time evaluated from rest-activity signals, rest-activity rhythm waveform and characteristics. The findings showed sleep-wake alterations of various degrees of severity, which in some patients did not parallel white blood cell counts in the cerebrospinal fluid. Actigraphic recording also showed improvement of the analyzed parameters after treatment initiation. Nocturnal polysomnography showed alterations of sleep time closely corresponding to those derived from actigraphy.

Conclusions/Significance

The data indicate that actigraphy can be an interesting tool for HAT evaluation, providing valuable clinical information through simple technology, well suited also for long-term follow-up. Actigraphy could therefore objectively contribute to the clinical assessment of HAT patients. This method could be incorporated into a clinical scoring system adapted to HAT to be used in the evaluation of novel treatments and laboratory biomarkers.

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NPL worked with Ecobrands Ltd to characterise their Zap-It! product, which uses the tiny electric current generated by piezoelectric material to relieve the pain and itching caused by insect bites – such as those from mosquitos.

Zap-It! is a pocket-sized product, marketed by Ecobrands, that is based around a similar piezoelectric mechanism to that used as the ignition source in electronic lighters. It is a medical device, currently available to buy in high street stores across the UK and Europe but, to be sold in the United States of America, it needs FDA (Food and Drug Administration) approval, which requires further test data regarding its electrical output.

Piezoelectric materials, the most well-known of which is quartz, produce a small electric current when their shape is deformed under pressure. By ‘clicking’ the Zap-It! device, an electrical current is produced that acts on the skin of an insect bite victim to reduce excess production of histamine, and the associated redness and itching. Results from a clinical trial conducted at the London School of Hygiene and Tropical Medicine concluded that more than 90% of test subjects were itch-free within five minutes of using the Zap-It! product.

Ecobrands contacted NPL as they were keen to collect as much accurate data as possible to submit to the FDA and to consider every aspect of their product’s safety. A Technology Innovation Fund project was set up to provide this data and potentially open up the US market to the product.

NPL has an international reputation in functional materials characterisation, especially that of piezoelectrics, and so was well positioned to carry out this work for Ecobrands. The majority of the measurements made in the project related to quantifying the electrical output from the device during normal operation. The main challenges came from the fact that the electric pulses produced are very high voltage, low current and are discharged over a short period of time – only 10 millionths of a second. The energy in these pulses depends on the load resistance and the device needed to be tested against a range of loads, representing different skin impedances, to ensure that the device output is safe in all possible conditions.

Robin Baker, Managing Director of Ecobrands, said: “It has been a privilege to have the opportunity to work with the team at NPL to dig deeply into the minutiae of the electrical world of the simple piezo. In my case, to fathom its application on the skin for remedial purposes, and confirm its function within accepted safety limits. With the detailed work Dr. Mark Stewart has produced, I hope Ecobrands will convince the FDA medical board that the product may be sold in the United States.”

An unprecedented collection of condom use studies, published in the journal Sexual Health, provides a global perspective on condom use problems and errors, along with new research on factors influencing correct condom use, how condom use programs can be more effective, and the promotion of the female condom. Led by The Kinsey Institute Condom Use Research Team, or CURT, more than 20 researchers from around the world examine and discuss issues such as safe-sex behaviors by American adults, counterfeit condoms in China and use of female condoms in South Africa.

“The articles in the special issue illustrate both commonalities and differences relative to the use and promotion of male condoms around the world,” said William L. Yarber, professor of applied health science at IU and member of CURT. “It provides a resource for sexual health professionals to use for strategizing ways to increase cultural and individual acceptance of condom use.”

The special issue appears online in advance of publication in the print issue. CURT, which has studied condom use for a decade, is a research team of scholars from Indiana University, the University of Kentucky, the University of Guelph in Ontario, Canada, and the University of Southampton in the United Kingdom.

The CURT researchers suggest that closing the gap between the ideal way condoms should be used and the more typical manner is critical to reducing unplanned pregnancies and the spread of sexually transmitted infections such as HIV. Condoms are inexpensive compared to costly HIV and AIDS medications, which often are inaccessible to the people most at risk.

“While we’d like to think the AIDS epidemic is going away, it’s not. In the U.S, it’s getting worse,” said Richard Crosby, a member of CURT, professor at the University of Kentucky and lead editor for Sexual Health’s special issue. “We keep looking to medical doctors for the solution to the epidemic, but it’s the wrong paradigm. We can prevent small pox, SARS, cholera and a host of other infectious diseases. The prevention of the disease is the modern solution to the AIDS pandemic, and we need to begin applying that solution in earnest.”

The special issue represents the first time condom use research from around the globe has been compiled in one place. CURT researchers want to get the information into the hands of global AIDS prevention organizations, such as the World Health Organization and the Centers for Disease Control and Prevention in the U.S.

“Condoms are the vaccine we’ve been waiting for,” Crosby said.

He said the gap between the correct use of condoms and the more typical use, which increases its fail rate, points to a need for better education and instruction regarding condom use. Making condoms accessible to people who need them is important, but improved clinic-based counseling, public education and Internet-based education efforts are all key requirements to their correct use. This involves talking openly about such things as erections, semen, lubricant and other aspects of sex that can make people uncomfortable. Crosby said this lack of education and detail because of embarrassment or discomfort comes at the cost of individuals’ health and lives.

“We chronically underestimate how complicated condom use can be,” he said. “It involves the use of a condom, while negotiating the condom use and sex with a partner all at the same time. There is a complex triad of the sex act, condom use and partner dynamics that must constantly be navigated by condom users.”

The research articles highlight problems and barriers to effective condom use and make suggestions for improving access to condoms, addressing cultural issues that can interfere with their efforts, specific populations that should receive more attention programmatically, and areas where more research is needed.

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Background

In late-stage palliative cancer care, relief of distress and optimized well-being become primary treatment goals. Great strides have been made in improving and researching pharmacological treatments for symptom relief; however, little systematic knowledge exists about the range of non-pharmacological caregiving activities (NPCAs) staff use in the last days of a patient’s life.

Methods and Findings

Within a European Commission Seventh Framework Programme project to optimize research and clinical care in the last days of life for patients with cancer, OPCARE9, we used a free-listing technique to identify the variety of NPCAs performed in the last days of life. Palliative care staff at 16 units in nine countries listed in detail NPCAs they performed over several weeks. In total, 914 statements were analyzed in relation to (a) the character of the statement and (b) the recipient of the NPCA. A substantial portion of NPCAs addressed bodily care and contact with patients and family members, with refraining from bodily care also described as a purposeful caregiving activity. Several forms for communication were described; information and advice was at one end of a continuum, and communicating through nonverbal presence and bodily contact at the other. Rituals surrounding death and dying included not only spiritual/religious issues, but also more subtle existential, legal, and professional rituals. An unexpected and hitherto under-researched area of focus was on creating an aesthetic, safe, and pleasing environment, both at home and in institutional care settings.

Conclusions

Based on these data, we argue that palliative care in the last days of life is multifaceted, with physical, psychological, social, spiritual, and existential care interwoven in caregiving activities. Providing for fundamental human needs close to death appears complex and sophisticated; it is necessary to better distinguish nuances in such caregiving to acknowledge, respect, and further develop end-of-life care.

Please see later in the article for the Editors’ Summary

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J Bioterror Biodef. 2011 Sep 25;S1(4)

Authors: Marzi A, Feldmann H, Geisbert TW, Falzarano D

Abstract

Ebola and Marburg viruses are emerging/re-emerging zoonotic pathogens that cause severe viral hemorrhagic fever with case-fatality rates up to 90% in humans. Over the last three decades numerous outbreaks, of increasing frequency, have been documented in endemic regions. Furthermore, as a result of increased international travel filovirus infections have been imported into South Africa, Europe and North America. Both viruses possess the potential of being used as bioterrorism agents and are classified as category A pathogens. Currently there is neither a licensed vaccine nor effective treatment available, despite substantial efforts being d́edicated to understanding filovirus well as vaccine and drug development. One of the most promising vaccine platforms is based on replication competent recombinant vesicular stomatitis viruses (rVSV) that express a filovirus glycoprotein as the surface antigen. These rVSVs have been extensively studied in rodent and nonhuman primate models of filovirus disease and, in general, have been shown to be 100% protective in pre-exposure prophylaxis. In addition, rVSVs have demonstrated potential for post-exposure treatment, and thus would be particularly useful in the event of intentional release as well as accidental exposures in outbreak and laboratory settings.

PMID: 22288023 [PubMed - as supplied by publisher]

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