Archive for juillet 2014

Injectable artesunate: cure or killer

juillet 9, 2014

By Irene Teis, 27 June 2014

A document in Scientific American (June 2014) describes the activities of MVV Medecines for Malaria Ventures, a « non profit » organization (association sans but lucratif) located at Geneva. It is surprising to learn that they sell Artesunate in monotherapy for intravenous injection at high doses ; in cooperation with WHO and Médecins sans Frontières.

Artemisinin derivatives not only lead to resistance, widespread in Africa now. N Van Hong and U. d’Alessandro in Emerging Infect Dis. Jul 2014 describe the case of a man with severe malaria who does not respond to intravenous artesunate. But these chemical derivatives also lead to strong side effects at high doses. Haemolytic, hepatotoxic, cytotoxic, neurotoxic, cardiotoxic, genotoxic, ototoxic, embryotoxic, spleenotoxic effects have been described in on October 19 2013. A recent paper from Germany T Rolling et al., Malaria Journal2012, 11 :169) describes post-treatment haemolysis by intravenous artesunate for three patients with pararasitaemia. The effect appears 2-3 weeks after the treatment.
Several other research teams have seen strong evidence for the same haemolytic anemia caused by IV artesunate.
– Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium . Annemarie R Kreeftmeijer-Vegter12*,Malaria Journal, 11:102 doi:10.1186/1475-2875-11-102, 2012.
– Severe malaria, artesunate and haemolysis, Pietro Caramello, Journal of Antimicrobial Chemotherapy Volume 67, Issue 8 Pp. 2053-2054. 2012.
– Artemisin-based combination therapies and their introduction in Japan, S Kano, Infect Chemother 16(6) : 375-382, 2010.

How is it possible that this product is still on the market ? An affected person in Germany will be recovered by the intense care described in the paper from T Rolling in Malaria Journal. But what about an African child returning home with his mother in the belief that the child has been cured ?

Why are African governments put under pressure not to use oral or rectal artesunate ? Why does WHO veto clinical trials with herbal medicinelike Artemisia afra ? Is it to protect this monopolistic business of injectable artesunate run by MMV, WHO and MSF ?

As Wallace Peters said : » I dissipated much energy in my younger days to scrape up funds for my research teams. Today, if you open the right tap, money can flow like water… »

Antiretrovirals and antimalarials: a deadly mix?

juillet 9, 2014

July 8, 2014 — Pierre Lutgen

At the 15th International Workshop on Clinical Pharmacology of HIV on May 19, 2014 at the University of Nebraska, FA Fehintola showed that nevirapine co-prescribed with artemether-lumefantrine may reduce the artemether concentration in blood by 70%.
This is in line with similar results obtained in South Africa by T Kredo (Antimicrob Agents Chemother. 2011 Dec; 55(12):5616-23). Artemether and nevirapine are metabolized by the cytochrome P450 3A4 enzyme system, which nevirapine induces. They conclude that studies investigating the interaction of nevirapine and artemether-lumefantrine in HIV-infected patients with malaria are urgently needed.
Pauline Byakik at Makerere University also found that co-administration of coartem (AL) with efavirenz resulted in reduction in artemether, DHA, lumefantrine exposure. (J Antimicrob Chemother 2012, 67, 2213-2221).

The antagonistic effect has not only been seen for artemisinin derivatives but also for quinine pharmacokinetics in pregnant women with Malaria-HIV Co-Infection (K Kayentao, Am J Trop Med Hyg. 2014 Mar;90(3):530-4).
Also for malarone frequently taken by European travellers. Lower atovaquone/proguanil concentrations have been found in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir (van Luin M1, AIDS. 2010 May 15;24(8):1223-6).
A good summary of these recent studies is given by Van Geertruyden JP. (Clin Microbiol Infect. 2014 Apr;20(4):278-85). Possible pathophysiological, clinical and epidemiological interactions between human immunodeficiency virus (HIV) and tropical pathogens, especially malaria parasites, constitute a concern in tropical areas. Two decades of research have shown that HIV-related immunosuppression is correlated with increased malaria infection, burden, and treatment failure, and with complicated malaria, irrespective of immune status. The recent role out of antiretroviral therapies and new antimalarials, such as artemisinin combination therapies, raise additional concerns regarding possible synergistic and antagonistic effects on efficacy and toxicity.

Already in 2006 F Nosten and U d’Alessandro had claimed that it was urgent to study drug interactions betweeen antimalarials and antiretrovirals, especially during pregnancy ( Curr Drug Saf 2006, Jan 1-15). Not much has been done until 2012.
But over the last decade millions of antimalarial and antiretroviral drugs for billions of dollars have been sold on the African market.
Cui bono ?

Comment by Valentine Lah
9 July 2014
I personally know so many HIV/AIDS patients under antiretroviral
therapy who keep drinking artemisia tea because they feel better and
stronger with it. I do not think that would have been the case if
there was a negative interaction between ARVs and natural Artemisia.