The human gut microbiota has become the subject of extensive research in recent years and our knowledge of the resident species and their potential functional capacity is rapidly growing. Our gut harbours a complex community of over 100 trillion microbial cells which influence human physiology, metabolism, nutrition and immune function while disruption to the gut microbiota has been linked with many diseases.
ARACHIDONIC ACID AND FEVER
Arachidonic acid (AA or ARA) is an extremely important fatty acid involved in cell regulation. It is a polyunsaturated fatty acid (20:4n6) covalently bound in esterified form in membrane phospholipids of most body cells. Following irritation or injury, arachidonic acid is released and oxygenated by enzyme systems leading to the formation of an important group of inflammatory mediators, to the prostaglandins products (PGE₂) by the cyclooxygenase enzyme.
Lors de la conférence du 19 mai 2014 à l’Université du Nebraska qui portait sur le SIDA, F.A. Fehintola montrait que la nevapirine prescrite simultanément avec l’artemether-lumefantrine (Coartem) réduisait de 70% la concentration du principe actif lumefantrine dans le sang infecté.
Ceci ne fait que confirmer des résultats obtenus en Afrique du Sud (T Kredo , Antimicrob Agents Chemother. 2011 Dec; 55(12):5616-23). L’artemether et la nevapirine sont métabolisés par le cytochrome P450 3A4 induit par la nevapirine.
A paper from Mali published last week is alarming (AA Djimbe et al., Parasite, 2016. 23, 3). Artesunate does not clear mature gametocytes during oral artesunate treatment and does not prevent the appearance of new gametocytes. This confirms to a large extent the randomized, double blind, large scale clinical trials of Munyanga and Idumbo in Maniema-Congo end of last year (see www.malariaworld.org).
In parallel with the clinical trials run by a team of medical doctors in the province of Maniema on the efficiency of Artemisia annua and Artemisia afra against malaria, (see Breaking News Jan.5 on www.malariaworld.org) they have completed another large scale randomized, double blind trial against schistosomiasis, Artemisia vs Praziquantel.
Artemisia plants are rich in polyunsaturated fatty acids (PUFA) which generate prostaglandins and stimulate monocytes. PUFAs possess well documented antimalarial and prophylactic properties. Their half-life in plasma is several days and in adipose tissue several weeks. This may explain the prophylactic effect of regular consumption of Artemisia infusion or powder.
From the recent reports out of California and other places, it appears that anophelines can be genetically modified so that (1) they are no longer susceptible to plasmodium infections, and (2) their progeny will be all males! If this can be developed for field use, it looks to me like it is the Beginning of the End of malaria in Africa. But I am an engineer with no experience in genetics. Do you think that this technique can be developed for field application?
A team of medical doctors in RDCongo, Jerome Munyangi and Michel Idumbo, have run randomized clinical trials on a large scale in the Maniema province with the participation of some 1000 malaria infected patients. The trials were run in conformity with the WHO procedures and compared Artemisia annua and Artemisia afra with ACTs (Coartem and ASAQ). For all the parameters tested herbal treatment was significantly better than ACTs: faster clearance for fever and parasitemia, absence of parasites on day 28 for 99.5% of the Artemisia treatments and 79.5% only for the ACT treatments.
H₂O₂ is omnipresent in plants and animals.
A recent report from a laboratory in California offers the hope for a method of genetic modification which could lead to species elimination from large geographical areas, such as Anopheles gambiae elimination from Africa. To quote the New York Times Science section of 22 December, “A gene drive designed to render a population extinct is known as a crash drive. A crash drive being developed for mosquitoes consists of a gene engineered into the Y chromosome that shreds the X chromosome in the cells that make the mosquito’s sperm, thus ensuring that all progeny are male.
As stated in previous blogs diabetes is on the rise everywhere. It is a debilitating and often fatal disease per se but it also increases the incidence of malaria because higher glucose contents in the blood are a fertile terrain for Plasmodium falciparum.
Diabetes burden is rising sharply in the African Region according to Dr Matshidiso Moeti, the WHO Regional Director for Africa. Reports of type 2 diabetes in children – previously rare – is a growing concern. In some countries, children and adolescents account for almost half of all newly diagnosed cases of type 2 diabetes. Diabetes is a leading cause of blindness, amputation, kidney failure and heart disease.
This quarterly report, produced by Vector Works, is meant to update the malaria community in general, and particularly those interested in vector control, on recently published research related to the improvement or development of new or alternative vector control tools. The report summarizes relevant new studies and highlights possible interpretations and implications, and it provides links to the original work. Aspects of indoor residual spraying are not included here as they are addressed in another newsletter (http://www.africairs.net). Read on to discover the exciting new contributions to the vector control field.
Rosine D. Chougouo NKuitchou1, Ernest Djoko1, Jonas Kouamouo1, Diane F. Domko1, Pierre Tane2, Denis Wouessidjewe1,3.
1 Faculty of Pharmacy, Université des Montagnes »P O Box 208 Bangangte, Cameroon 2 Laboratory of Natural Products Chemistry, Faculty of Sciences, University of Dschang P O Box 67 Dschang Cameroon 3 UFR of Pharmacy, Department of Molecular Pharmacochemistry, University of Joseph Fourrier of Grenoble PO Box 53 38041 Grenoble Cedex 9.
The amino acid arginine is the only molecule in our food known to generate nitric oxide NO via NOS enzymes. It plays a key role in malaria therapy and cerebral malaria as described in previous blogs on www.malariaworld.org. NO derived from arginine is not only lethal for merozoites but also for gametocytes. NO is efficient against other diseases like leishmaniasis or filariasis (R O’Connor et al., Infection and Immunity, 2000, 68, 6101-6107).
The MESA Track database is now one year old. Thanks to your collaboration, the database has grown to 700 projects over the past year. MESA Track is an open and online platform for sharing information on current research projects relevant to malaria elimination.
More than 25 institutions from across the world have shared their full research portfolio in MESA Track, including institutions working on basic science, product development and operational research.
Our partners at the Al Quds University in Palestine have found that a zinc-arginine complex strongly inhibits beta-hematin crystallization, like quinine does, but that zinc or arginine alone are not effective. Arginine and zinc play an important role in the human physiology. The plants from the Artemisia family are rich in these constituents which play probably a key role against malaria and other diseases. They easily form a complex in a large range of reagent concentrations (E Bottari et al., Monatshefte Chemie 2014, 145, 1707-1714).
A blog posted on www.malariaworld.org on June 21. 2014 « Aspirin and artemisinin, beware » and another one on July 8 of the same year « Antiretrovirals and antimalarials : a deadly mix » had already highlighted the fact that drugs sold on a large scale in Africa showed strong antagonism with several antimalarial drugs. ARVs reduce the concentration of artemether , quinine, malarone in the blood. Aspirin has an effect on the endothelium and platelet adherence.
A paper published twenty years ago should have attracted more attention (NM Anstey et al., J Exp Med 1996, 184, 557-567) : the suppression of NO synthesis in cerebral malaria appears to enhance pathogenesis and increased NO synthesis protects against clinical disease. The work was based on in vivo results obtained in Tanzanian children. Already five years earlier the killing of Plasmodium falciparum in vitro by nitric oxide derivatives (NO, nitrite, nitrate) had been demonstrated (KA Rockett et al., Infection and Immunity, 1991, 59, 3280-3283).
Save the Date for the 2017 Keystone Symposia - February 19-23, 2017, Kampala (Uganda) - conference on:
Malaria: From Innovation to Eradication
Organized in collaboration with MESA, this symposium provides a space for malaria eradication scientists to share new information and advance the scientific debate.
Plasmodium falciparum generates substantial amounts of ammonia as a metabolic by-product, but lacks detoxification mechanisms (S Kimoloi et al., Hypothesis and Theory, 2015, 9,article 234). It imports large amounts of glutamine from the host serum. Deamidation and deamination reactions generate two molecules of ammonia per glutamine molecule, particularly in the early trophozoite stages (T Zeuthen et al., Mol Microbiol 2006, 61, 1598-608).
The message below, from Dr. Pedro Alonso, the Director of WHO's Global Malaria Programme was circulated today, 24 October 2015.
Last month there was great news for the malaria world: A detailed analysis of the impact of insecticide-treated bednets (LLINs), ACTs, and indoor residual spraying (IRS), showed that some 6.2 million deaths and 700 million cases were averted between 2000-2015, mostly since 2005. Add up the contribution of the vector control components, and it shows that 78% of all the gains originated from just these two tools: LLINs and IRS. Is it safe to draw the conclusion from this that vector control is and shall remain the integral and critical component that will lead us to a world without malaria by 2040? I think the answer to that is 'yes, very much so'.