Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-02603-z
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Funding
- Johns Hopkins Malaria Research Institute Pilot grant
- Bloomberg Philanthropies
- National Institutes of Health [T32GM066691, R24AI118397, R01AI114405-01]
- Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases
- Engineering and Physical Science Research Council [EP/G066272/1, EP/K002201/1, EP/L02635X/1]
- [R01AI095453]
- EPSRC [EP/G066272/1, EP/K002201/1, EP/L02635X/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/K002201/1, EP/L02635X/1, EP/G066272/1] Funding Source: researchfish
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI114405, R01AI095453, R24AI118397] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM066691] Funding Source: NIH RePORTER
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Chemoprophylaxis is currently the best available prevention from malaria, but its efficacy is compromised by non-adherence to medication. Here we develop a long-acting injectable formulation of atovaquone solid drug nanoparticles that confers long-lived prophylaxis against Plasmodium berghei ANKA malaria in C57BL/6 mice. Protection is obtained at plasma concentrations above 200 ng ml(-1) and is causal, attributable to drug activity against liver stage parasites. Parasites that appear after subtherapeutic doses remain atovaquonesensitive. Pharmacokinetic-pharmacodynamic analysis indicates protection can translate to humans at clinically achievable and safe drug concentrations, potentially offering protection for at least 1 month after a single administration. These findings support the use of longacting injectable formulations as a new approach for malaria prophylaxis in travellers and for malaria control in the field.
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