Archive for mars 2014

Are in vitro antimalarial assays a waste of time?

mars 24, 2014

 

 

Most of the assessments on the antimalarial efficacy of a molecule are made in vitro. In the case of plant material the first step is generally the extraction with an organic solvent. The extract is then lyophilized, frozen and stored for subsequent trials.

 

A recent research paper from the University of Al Quds (M Akkawi et al., Med Aromat Plants, 2014, 3:1) showed that lyophilized extracts lost activity with time, which may have an impact not only on in vitro laboratory results but also in vivo treatment efficiency obtained with old extracts or molecules contained within.

 

Furthermore, these extracts obtained with organic solvents miss the molecules contained in a plant which are only water soluble, like polysaccharides. And when water is used it is ultrapure water which has nothing to do with the tap or well water the infected person is going to use for the ingestion. pH and ionic strength of the water have an effect on solubility and pharmacodynamics.

 

The extracts are generally passed through filters with ultrafine pore sizes, which will remove all kinds of bulky molecules like polysaccharides or their aggregates. In the next step most research efforts will try to fractionate the extract in its individual molecules to assess the efficacy of each one isolated.

 

It is unfortunate that in vivo results obtained with these isolated molecules will lead to monotherapies as it is the case with artemisinin and its derivatives. It does not make much sense to add a second molecule like amodiaquine which has already shown severe signs of resistance since more than twenty years. It is putting two leaking buckets on into the other. A well designed booby trap for Africans.

 

A growing body of studies, especially those of P Weathers (M A Elfawal et al., Plos One, Dec 2012, 7:12, e52746)  have shown that compared to pure artemisinin, delivery of the drug via oral consumption of dried Artemisia annua leaves better fights parasitemia, delivers far more of the drug into the blood, persists longer in the blood of infected animals than healthy ones, requires far less of the drug to get a better therapeutic effect, and is safe and effective in human malaria patients. Furthermore, the dried plant offers a plethora of other endogenous chemicals that could well thwart emergence of drug resistance; many show some anti-plasmodial efficacy. Some work in concert with artemisinin.

There are claims that use of tea or dried leaves is just monotherapy and will cause artemisinin drug resistance. But these claims never have been assessed by clinical trials…thus nobody knows. It is crucial that decisions affecting millions of lives be made on solid scientific facts and not just on fearful conjecture.

The debate on in vitro versus in vivo is linked to the debate on efficacy versus effectivenes. Ideally one can only talk about efficacy in laboratory conditions because the experiment can be fully controlled. Measuring plasma levels of drug alone is not sufficient for efficacy because many other factors such as food, immune status, environment, genetics etc influence drug efficacy. Therefor effectiveness describes the real life situation but the problem is that mathematically we cannot compute real life situations and this is why most studies compute and report efficacy by having treatment group versus control group data compared. Even then inter human and intra human variations cannot be completely controlled.

Some compounds exist in what we call pro-drugs, they need to be activated by some enzyme system in order to become active. In vitro tests miss such drugs because they lack the enzyme system or related factor. Actually most plant medicines have been wrongly lost by relying on in-vitro systems when they show negative results. Also some compounds may be active in vitro but have zero effect in in-vivo because the body may have enzyme system that destroys it before it produces effect. A human body is complex and no one understands it fully. Even if in vitro you have a fantastic efficacy  you may have a negligible efficiency in vivo. Or often the reverse: you may have zero efficacy in vitro but still a high in vivo efficacy.

Some drugs are just designed to kill the parasites released into the blood stream, but they leave a bloody battlefield and a depressed immune system.

Repeated malaria attack results into excess haemozoin produced by parasites when they digest the haemoglobin for their food. Accumulation of haemozoin in blood weakens the white blood cells that help in mopping out of malaria parasites after treatment. There is no drug that eliminates all the infections from ones body. Drugs help to reduce the parasite load and our immune system does the mop up. So if the immune system is weak, the residual parasites are not removed and the infection surges again causing malaria.

 

Patrick Engeu Ogwang                                                                     Pierre Lutgen

 

IPCC, climate and malaria: scaremonging or ignorance

mars 11, 2014

 

 by Irene Teis

I was flabbergasted to find on the generally sound www.malariaworld.org a flurry of press releases relating malaria to climate change.

This is nonsense. Malaria is not a tropical disease. It was common throughout Europe, not only in Spain, Sardinia, Greece but as far North as the Baltic and northern Russia. Siberia registered 600 000 deaths due to Plasmodium falciparum in 1920. Falciparum malaria was common in Europe during the Little Ice Age 5 centuries ago. Activist organizations, such as the World Wildlife Fund and Greenpeace, continue to quote the IPCC statement that malaria can only be transmitted in regions where winter temperatures are above 16ºC. Al Gore’s absurdities.

Malaria has been wiped out in the US and in Europe mostly by DDT. The WHO declared Holland malaria-free in 1970. But then the battle ended and Africa was left alone. A genocide resulted !

Prof  P. Reiter, Institut Pasteur, Paris,  in a paper published in  Malaria Journal 7 (2008) “Global warming and malaria: Knowing the horse before hitching the cart” criticizes very well the nonsense generated by computer modelling. Fast food for the popular press!

P. Reiter  has been a member of the WHO Expert Advisory Committee on Vector Biology and Control since 1998, and a consultant for several WHO Scientific Working Groups.

In a Memorandum which can be found on internet he explains his disappointment with the operating practices of IPCC. The third assessment report in its health chapter cites more than 65 lead authors. Only 3 were an established authority on vector-borne disease.

“After much effort and many fruitless discussions, I decided to resign from the IPCC project. My resignation was accepted, but in a first draft I found that my name was still listed. I requested its removal, but was told it would remain because « I had contributed ». It was only after strong insistence that I succeeded in having it removed…

In my opinion the IPCC has done a disservice to society by relying on “experts” who have little or no knowledge of the subject…

Alarmist activists operating in well-funded advocacy groups have a lead role in creating this misinformation.

We would be better off redirecting the millions spent on climate change research to preventing diseases such as malaria. “

 irene.teis@gmail.com

HÔPITAL SANS FRONTIÈRES NOUS AIDE AU KATANGA

mars 8, 2014

 

Rotary helps African doctors

 
Depuis plus d’une année l’ONG http://www.iwerliewen.org travaille avec une équipe de médecins du Tumaini Center de Lubumbashi. Leur champ d’action sont de petits dispensaires de campagne souvent très mal équipés. Cette même équipe a mené à bien plusieurs essais cliniques qui ont montré l’efficacité extraordinaire contre le paludisme de gélules contenant de la poudre d’Artemisia annua. Les derniers essais ont porté sur l’Artemisia afra, une plante indigène, qui se montre efficace également, tout en ne contenant pas la molécule artemisinine. Hôpital sans Frontières est une association créée par des Rotariens de Namur. Nous avons pu visiter leurs hangars qui regorgent de matériel clinique de seconde main, mais de bonne qualité. Ils ont mis à notre disposition une valise de matériel léger comme celui de la photo. Matériel que nous allons acheminer vers Lubumbashi grâce à l’aide de l’entreprise de transport Sales-Lentz de Luxembourg.