Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination.
Achieving a theoretical foundation for malaria elimination will require a detailed understanding of the quantitative relationships between patient treatment-seeking behavior, treatment coverage, and the effects of curative therapies that also block Plasmodium parasite transmission to mosquito vectors. Here, we report a mechanistic, within-host mathematical model that uses pharmacokinetic (PK) and pharmacodynamic (PD) data to simulate the effects of artemisinin-based combination therapies (ACTs) on Plasmodium falciparum transmission. To contextualize this model, we created a set of global maps of the fold reductions that would be necessary to reduce the malaria R C (i.e. its basic reproductive number under control) to below 1 and thus interrupt transmission. This modeling was applied to low-transmission settings, defined as having a R 0<10 based on 2010 data. Our modeling predicts that treating 93-98% of symptomatic infections with an ACT within five days of fever onset would interrupt malaria transmission for ∼91% of the at-risk population of Southeast Asia and ∼74% of the global at-risk population, and lead these populations towards malaria elimination. This level of treatment coverage corresponds to an estimated 81-85% of all infected individuals in these settings. At this coverage level with ACTs, the addition of the gametocytocidal agent primaquine affords no major gains in transmission reduction. Indeed, we estimate that it would require switching ∼180 people from ACTs to ACTs plus primaquine to achieve the same transmission reduction as switching a single individual from untreated to treated with ACTs. Our model thus predicts that the addition of gametocytocidal drugs to treatment regimens provides very small population-wide benefits and that the focus of control efforts in Southeast Asia should be on increasing prompt ACT coverage. Prospects for elimination in much of Sub-Saharan Africa appear far less favorable currently, due to high rates of infection and less frequent and less rapid treatment.
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York, United States of America ; School of International and Public Affairs, Columbia University, New York, New York, United States of America ; Bloomberg School of Public Health, John Hopkins University, Baltimore, Maryland, United States of America.
Geoffrey L
GL
Johnston
Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, United Kingdom.
Peter W
PW
Gething
Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, United Kingdom.
Simon I
SI
Hay
Bloomberg School of Public Health, John Hopkins University, Baltimore, Maryland, United States of America.
David L
DL
Smith
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York, United States of America ; Division of Infectious Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, United States of America.
David A
DA
Fidock
D000465:Algorithms; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001210:Asia, Southeastern; D003140:Communicable Disease Control; D003198:Computer Simulation; D009033:Culicidae; D005843:Geography; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology / Q000635:transmission*; D008962:Models, Theoretical; D010963:Plasmodium falciparum / Q000187:drug effects*; D012984:Software
D000962:Antimalarials