https://www.sciencedaily.com/releases/2018/01/180119090342.htm

Promising malaria medication tested
New combination of drugs proves effective and well-tolerated; further studies planned

January 19, 2018

Universitaet Tübingen

Summary:
An international research team has conducted successful phase II clinical tests of a new anti-malaria medication. The treatment led to a cure in 83 cases.

FULL STORY

Researchers tested the efficacy, tolerability and safety of a combination of the drugs Fosmidomycin and Piperaquine. 

An international research team has conducted successful phase II clinical tests of a new anti-malaria medication. The treatment led to a cure in 83 cases. The new combination of drugs was developed by Professor Peter Kremsner of the Tübingen Institute of Tropical Medicine and the company DMG Deutschen Malaria GmbH. The study was recently published in Clinical Infectious Diseases and is freely accessible.

In the study, the researchers tested the efficacy, tolerability and safety of a combination of the drugs Fosmidomycin and Piperaquine. The twofold medication was administered for three days to patients aged one to thirty who were infected with malaria via the Plasmodium falciparum pathogen. In the 83 evaluable cases, there was a 100% cure rate. Patients tolerated the treatment well, and it led to a swift reduction of clinical symptoms. Safety issues were limited to changes in electrocardiogram readings, as had been described for Piperaquine.

The study was conducted at the Centre de Recherches Médicales de Lambaréné (CERMEL) in the African country of Gabon; CERMEL has close ties with the University of Tübingen. Financial support came from the nonprofit organisation Medicines for Malaria Venture (MMV).

“This study represents a milestone in the clinical research into Fosmidomycin,” says Tübingen Professor of Tropical Medicine Peter Kremsner. The substance was originally extracted from Streptomyces lavendulae and today can be produced synthetically. It blocks a metabolic pathway for the production of Isoprenoid in the malaria pathogen. This makes the malaria pathogen unable to metabolize or reproduce. Because Isoprenoids are formed via a different synthesis path in the human body, humans have no target structures for Fosmidomycin. For this reason humans tolerate the drug well and suffer barely any side effects. In addition, this unique mechanism excludes the possibility of cross-resistance to the drugs used in earlier malaria treatments.

The new combination meets WHO guidelines for combination therapies. The two drugs mechanisms against differing target structures means that they attack the parasite in the bloodstream independently of one another. This meets WHO requirements for a fast and effective treatment of the acute phase of infection, and for protection against relapse due to reappearance of the infection. The researchers say the effective mechanism helps to delay the formation of a possible resistance. Further studies are in planning to optimize dose.

Journal Reference:

Ghyslain Mombo-Ngoma, Jonathan Remppis, Moritz Sievers, Rella Zoleko Manego, Lilian Endamne, Lumeka Kabwende, Luzia Veletzky, The Trong Nguyen, Mirjam Groger, Felix Lötsch, Johannes Mischlinger, Lena Flohr, Johanna Kim, Chiara Cattaneo, David Hutchinson, Stephan Duparc, Moehrle Joerg, Thirumalaisamy P Velavan, Bertrand Lell, Michael Ramharter, Ayola Akim Adegnika, Benjamin Mordmüller, Peter G Kremsner. Efficacy and safety of fosmidomycin-piperaquine as non-artemisinin-based combination therapy for uncomplicated falciparum malaria – A single-arm, age-de-escalation proof of concept study in Gabon. Clinical Infectious Diseases, 2017; DOI: 10.1093/cid/cix1122

https://clinicaltrials.gov/ct2/show/NCT02198807    Evaluation of Fosmidomycin and Piperaquine in the Treatment of Acute Falciparum Malaria (FOSPIP)
Verified June 2015 by Jomaa Pharma GmbH.

Collaborator:
Centre de Recherche Médicale de Lambaréné

Brief Summary:
The objective of this study is to explore the role of fosmidomycin and piperaquine as non-artemisinin-based combination therapy for acute uncomplicated Plasmodium falciparum when administered over three days.
Together, fosmidomycin and piperaquine fulfil the WHO criteria for combination therapy by meeting the three key parameters of having different modes of action and different biochemical targets while exhibiting independent blood schizonticidal activity. Like the artemisinins, fosmidomycin is fast-acting, has an excellent safety record and is active against existing drug-resistant parasites. Piperaquine has a long half life protecting fosmidomycin as a much shorter lived molecule against selection of resistant parasites and will provide post-treatment prophylaxis.

Experimental: Fosmidomycin-Piperaquine
Fosmidomycin sodium capsules 450 mg, dosage: 30mg/kg twice daily for 3 days Piperaquine phosphate tablets 320 mg, dosage: 16 mg/kg once a day for 3 days

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**Comment**

It appears this works for Babesia as well:  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019334&bw=1  Babesia divergens, a related parasite that also infects human erythrocytes and is also known to induce an increase in membrane permeability, displays a similar susceptibility and uptake behavior with regard to the drug. In contrast, Toxoplasma gondii-infected cells do apparently not take up the compounds, and the drugs are inactive against the liver stages of Plasmodium berghei, a mouse malaria parasite.

The big caveat; however, is that many Lyme/MSIDS patients are persistently infected with Babesia and need far more than 3 days for acute treatment:  https://madisonarealymesupportgroup.com/2016/01/16/babesia-treatment/  Dr. Krause published in the New England Journal of Medicine that when a patient has Lyme and Babesia, Lyme is found three-times more frequently in the blood, proving Babesia suppresses the immune system.

Testing which is poor as these organisms are not often found in high enough numbers in the blood, as well as people present subclinically. In other words, their Lyme case is more severe and they have malarial-type symptoms, but they can’t find Babesia in the blood in a Giemsa stain. It takes a trained eye to identify Babesia, which produces a Maltese Cross form, which may or may not be present in a particular smear. Also, doctors have been taught that besides the day and night sweats and chills, patients are supposed to get hemolytic anemia and their liver functions go up or their platelet count might go down (thrombocytopenia). The fly in the ointment is that only certain strains of Babesia do this. Many strains do not cause these symptoms – but doctors aren’t educated on these finer points. Also, to hide from the immune system, the various species produce offspring that have different exterior proteins, or genotypes. http://www.townsendletter.com/July2015/babesia0715_2.html According to Dr. Schaller, there is immense variation and pre-2015 treatments were “weak and showed ignorance of the power of Babesia – it is vastly harder to kill than malaria.”