Mobile Technology Used to Fight Malaria Drug Counterfeiting

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African Social Enterprise mPedigree Networks has been running a program in Nigeria and Ghana that allows consumers to verify the authenticity of anti-malaria drugs by using mobile phone SMS technology. With the new service, patients taking a range of medication and send a free text message to get an instant response as to whether the medications are genuine.

Counterfeit medicines often contain the wrong quantity of active pharmaceutical ingredients, which can result in illness or death. The system assigns a code that is revealed by scratching off a coating on the drugs’ packaging. This code can be text messaged by the consumer or medical professional to a free SMS (short message service) number to verify the authenticity of the drug.

If the drug packaging contains a counterfeit code, the consumer will receive a message alerting them that the pack may be a fake, as well as a phone number to report the incident. Pharmaceutical safety regulators in Ghana and Nigeria are working to ensure that the concerns of users are promptly addressed.

“Counterfeit pharmaceuticals are a big problem for developing nations, particularly in Africa. It is important that we developed an African solution to an African problem, using the resources and technologies that are widely available and easy to implement,” said Bright Simons, founder, mPedigree Network. “It’s absolutely imperative that people can trust the authenticity of the drugs they are consuming, and this system will give them an easy and effective way of doing so.”

“Over the years, we have invested a huge amount of time and money in developing drugs which will protect the health of people around the world,” said Dr. Joseph Ikemefuna Odumodu, chief executive, May & Baker Nigeria, and president, West African Pharmaceutical Manufacturers Association. “It’s in both our and our customers’ interest that they receive the full benefit of that investment. This system will safeguard both of us now and in the future.”

HP is providing the hosting infrastructure for the service, as well as the security and integrity systems, through its data centers in Frankfurt, Germany. mPedigree Network is providing the business process interfaces that allow pharmaceutical companies to code their products for the system and to monitor use of genuine and counterfeit drugs.

The service, which was endorsed by the West African Health Organization, is expected to be available for other medications and in more countries in the near future. All GSM mobile network operators in Ghana and Nigeria are signatories to the scheme.

“Technology plays a critical role in solving many serious health problems around the world,” said Gabriele Zedlmayer, vice president, Office of Global Social Innovation, HP. “While Nigeria and Ghana are the starting points for this program, we are working to create a scalable infrastructure to be used by other regions where counterfeit medicine is a growing issue.”

In November 2010, mPedigree won the start-up category of the Global Security Challenge in London, becoming the first organisation in the Southern Hemisphere to win the award according to the organizers, and in February 2011, mPedigree won the 2011 Netexplorateur Grand Prix at UNESCO in Paris, for combating fake medicine in Africa through texting.

Sources: HP Press Release (12-10-10); Wikipedia (http://en.wikipedia.org/wiki/Mpedigree)
More information: mPedigree; BBC

ECOWAS Program to Eradicate Malaria

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QUESTION
Why can I find no mention on your website of the ECOWAS program to eradicate malaria in their countries?

ANSWER
Thanks for bringing up ECOWAS. Since 2011, ECOWAS leaders have signaled a commitment to eradicating malaria in their region by 2015, and pilot programs are already underway in several countries, including Burkina Faso, Nigeria and Ghana. The program has centered on the use of larvicides for control of mosquito populations, thus reducing transmission. In April 2012, ECOWAS signed an agreement with Cuba in order to revitalize joint efforts to eradicate malaria in both West Africa as well as the Caribbean island. Soon after, Venezuela entered the agreement, pledging $20 million to the cause. These funds
will help support the construction of manufacturing facilities for biolarvicides in Nigeria, Cote d’Ivoire and Ghana, among other things.

In August, the Commissioner of ECOWAS emphasized the need for community engagement in the fight against malaria. A road map for measuring future progress was also drawn up by health advisers from the region; the next high-level ministerial meeting to evaluate the program will take place in West Africa, and will likely include Cuban and Venezuealan partners, in December 2012.

WHO recommends that Larviciding is indicated only for vectors which tend to breed in permanent or semi-permanent water bodies that can be identified and treated, and where the density of the human population to be protected is sufficiently high to justify the treatment with relatively short cycles of all breeding places.

Severe Head Pain with Malaria

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QUESTION

Can severe head pain be a symptom of mistreated malaria? My son just returned from an 8 month trip to Ghana. He had malaria 3 times and typhoid 1 time. He is now dealing with a severe head pain in his frontal lobe.

He took doxycycline every day and when he got really sick, he took Coartem. He was finally sent home because they couldn’t figure out why he has such severe head pains. Where do we go from here? He has an MRI scheduled and an appointment with an Infectious Disease Doctor. I am afraid they will not know what to do to help him. I am seeking more advice. Hopeful…CT

ANSWER

Severe head pain is not associated with mistreated malaria, nor indeed is considered a possible lasting effect of malaria infection. You are doing the right thing by going to see a doctor, including one who is an infectious disease specialist—I hope they also have experience with tropical medicine, since in the US and Europe, many very well-trained doctors are still not very familiar with the types of infections which are more commonly observed in the tropics.

Your son was right to take Coartem when he had malaria, but do you know whether he went to a clinic for diagnosis first? The symptoms of malaria are very general, such as fever, chills, nausea and aches, and many people in malarial areas (particularly visitors) often assume they have malaria when in fact their symptoms could be caused by a number of other things.

Secondly, doxycycline is considered a very effective preventive medication against malaria, but only if taken properly. Since doxycycline can cause mild stomach upset, many people take it with milk, which can lessen these symptoms; however, the calcium in the milk can bind to the drug, preventing successful absorption and reducing its efficacy as a malaria preventive.

If your son had a diet high in diary products or took antacids while in Ghana, this could explain why he suffered several malarial episodes. Alternatively, if he took the drug regularly and correctly, and particularly if he did not seek diagnosis via blood test from a clinic, that may be an indication that he wasn’t suffering from malaria at all, and other causes should be explored.

Finally, one of the very well-described side effects of doxycycline is its tendency to cause people to become very sun sensitive. While this usually manifests itself in skin sensitivity, it could also be that your son has become more visually sensitive to light, which in itself could lead to severe headaches. I hope he feels better soon!

Malaria Prophylaxis in Ghana, Africa

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QUESTION

My husband will be traveling to Ghana soon. We have Mefloquine and Primaquine. Which one do you think is best for prophylaxis in Ghana? He also has Fansidar, but we understand it’s best not to use this for prophylaxis. Thank you for your help!

ANSWER

There are positives and negatives associated with both of these medications. Mefloquine is recommended for travelers in Ghana (whereas the Centers for Disease Control does not explicitly recommend primaquine for this area, since primaquine is particularly effective against Plasmodium vivax malaria, which is almost completely absent from West Africa), and only has to be taken once a week (primaquine must be taken daily).

A disadvantage with mefloquine is that you must start taking it 2 weeks before your trip, whereas primaquine can be started as little as 1-2 days before travel; mefloquine is also not recommended for people with a history of psychiatric or mental problems, as it can cause severe side effects. Even healthy individuals often report disturbing dreams or increased agression/anxiety while taking mefloquine. However, one major disadvantage to primaquine is that you must be tested for G6DP deficiency prior to taking it – your husband may have already done this, prior to being prescribed the drug. People with G6DP deficiency should not take primaquine.

Overall, the decision comes down to personal preference, though from a disease perspective, mefloquine would probably be the better choice for travel to Ghana, given the higher prevalence of P. falciparum malaria in this region, as opposed to P. vivax. Other options to consider would be atovaquone-proguanil (Malarone – expensive, taken daily, but very effective and very well tolerated by most people, with very low side effects) or doxycycline (very cheap, taken daily, is an antibiotic so can prevent some other infections but often results in sun sensitivity, which can be a problem in the tropics). Both of these can be started 1-2 days before arriving in the malarial area.

After you come back, I would be very grateful if you could take our malaria medication side effects survey, as we are very interested in hearing from our readers what their experiences with malaria prophylaxis and treatment have been.

Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria

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Human genetics and immune responses are considered to critically influence the outcome of malaria infections including life-threatening syndromes caused by Plasmodium falciparum. An important role in immune regulation is assigned to the apoptosis-signaling cell surface receptor CD95 (Fas, APO-1), encoded by the gene FAS.

Here, a candidate-gene association study including variant discovery at the FAS gene locus was carried out in a case-control group comprising 1,195 pediatric cases of severe falciparum malaria and 769 unaffected controls from a region highly endemic for malaria in Ghana, West Africa. We found the A allele of c.−436C>A (rs9658676) located in the promoter region of FAS to be significantly associated with protection from severe childhood malaria (odds ratio 0.71, 95% confidence interval 0.58–0.88, pempirical = 0.02) and confirmed this finding in a replication group of 1,412 additional severe malaria cases and 2,659 community controls from the same geographic area.

The combined analysis resulted in an odds ratio of 0.71 (95% confidence interval 0.62–0.80, p = 1.8×10−7, n = 6035). The association applied to c.−436AA homozygotes (odds ratio 0.47, 95% confidence interval 0.36–0.60) and to a lesser extent to c.−436AC heterozygotes (odds ratio 0.73, 95% confidence interval 0.63–0.84), and also to all phenotypic subgroups studied, including severe malaria anemia, cerebral malaria, and other malaria complications. Quantitative FACS analyses assessing CD95 surface expression of peripheral blood mononuclear cells of naïve donors showed a significantly higher proportion of CD69+CD95+ cells among persons homozygous for the protective A allele compared to AC heterozygotes and CC homozygotes, indicating a functional role of the associated CD95 variant, possibly in supporting lymphocyte apoptosis.

Author Summary

Severe malaria caused by infection with the protozoan parasite Plasmodium falciparum is a major health burden, causing approximately one million fatalities annually, predominantly among young children in Sub-Saharan Africa. The occurrence of severe malaria may depend on a complex interplay of transmission dynamics and the development of a protective immune response but also on heritable differences in the susceptibility to the disease.

In two large studies including a total of 2,607 affected children and 3,428 apparently healthy individuals from Ghana, West Africa, we investigated genetic variants of the FAS gene, which encodes CD95, a molecule critically involved in the programmed cell death of lymphocytes. We found that a single nucleotide variant in the FAS promoter was associated with a 29%–reduced risk of developing severe malaria. In individuals carrying two copies of the protective allele, a higher proportion of activated lymphocytes was found to express CD95. These findings indicate that a predisposition to an increased expression of CD95 may help to protect from severe malaria, possibly by rendering activated T-lymphocytes more susceptible to programmed cell death.

Citation: Schuldt K, Kretz CC, Timmann C, Sievertsen J, Ehmen C, et al. (2011) A −436C>A Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria. PLoS Genet 7(5): e1002066. doi:10.1371/journal.pgen.1002066

Editor: Daniel C. Jeffares, University College London, United Kingdom

Received: November 3, 2010; Accepted: March 18, 2011; Published: May 19, 2011

Copyright: © 2011 Schuldt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The work was supported by the German National Genome Research Network (NGFN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Authors: Kathrin Schuldt1,2*, Cosima C. Kretz3, Christian Timmann1,2, Jürgen Sievertsen1, Christa Ehmen1, Claudia Esser1, Wibke Loag4, Daniel Ansong5, Carmen Dering2, Jennifer Evans1, Andreas Ziegler2, Jürgen May4, Peter H. Krammer3, Tsiri Agbenyega5, Rolf D. Horstmann1

1 Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany, 2 Institute of Medical Biometry and Statistics, University at Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany, 3 Division of Immunogenetics, German Cancer Research Centre, Heidelberg, Germany, 4 Infectious Disease Epidemiology Group, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany, 5 School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

Full text: A −436C>A Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria (PDF)

Malaria Prevention for Seniors

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QUESTION:

I am a healthy senior citizen (73 years) and I am considering a trip with Semester at Sea. One of the ports they plan to visit is Ghana. I see the CDC says Ghana is a “high risk” area for malaria.

I think I remember being told (at the U of W Travel Medicine Clinic) a few years ago that the malaria drugs are problematic for Seniors.

With the Semester at Sea ship stopping at Takoradi, Ghana, how high a risk is malaria and what preventative measures could/should I take?

I have had no malaria treatment (preventive or due to illness) in the past.

Thank you.

ANSWER:

It is correct that Ghana is a high risk zone for malaria, and wise of you to investigate ways to prevent infection. This is especially the case given that there is evidence to suggest that senior citizens and travellers over the age of 60 may be more at risk of serious complications from malaria. As such, it is especially important for these high risk groups, which also includes pregnant women and children, to be well aware of ways to reduce the risk of exposure and infection.

Having said that, I have done some research and I don’t think there is any evidence that the standard drugs for preventing malaria work less well in older people. In fact, one study I found suggested that younger people were more likely to report side effects from taking malaria preventative medicine (see Mittelholzer et al., “Malaria prophylaxis in different age groups” in volume 3 of the Journal of Travel Medicine, published in 2006).

The only potential problem could be cross-reaction of the malaria drugs with other prescribed medicine. As such, I would recommend you enquire with your doctor prior to the trip, to ask about being prescribed drugs to prevent malaria that are appropriate for the region you are travelling to (probably Malarone, Lariam or doxycycline, since you will be travelling to an area with chloroquine-resistant forms of malaria) that furthermore won’t harmfully interact or have reduced efficacy when ingested alongside other medication you might already be taking.