A Sub-Microscopic Gametocyte Reservoir Can Sustain Malaria Transmission

PLOS ONE, Jun 2011

Background Novel diagnostic tools, including PCR and high field gradient magnetic fractionation (HFGMF), have improved detection of asexual Plasmodium falciparum parasites and especially infectious gametocytes in human blood. These techniques indicate a significant number of people carry gametocyte densities that fall below the conventional threshold of detection achieved by standard light microscopy (LM). Methodology/Principal Findings To determine how low-level gametocytemia may affect transmission in present large-scale efforts for P. falciparum control in endemic areas, we developed a refinement of the classical Ross-Macdonald model of malaria transmission by introducing multiple infective compartments to model the potential impact of highly prevalent, low gametocytaemic reservoirs in the population. Models were calibrated using field-based data and several numerical experiments were conducted to assess the effect of high and low gametocytemia on P. falciparum transmission and control. Special consideration was given to the impact of long-lasting insecticide-treated bed nets (LLIN), presently considered the most efficient way to prevent transmission, and particularly LLIN coverage similar to goals targeted by the Roll Back Malaria and Global Fund malaria control campaigns. Our analyses indicate that models which include only moderate-to-high gametocytemia (detectable by LM) predict finite eradication times after LLIN introduction. Models that include a low gametocytemia reservoir (requiring PCR or HFGMF detection) predict much more stable, persistent transmission. Our modeled outcomes result in significantly different estimates for the level and duration of control needed to achieve malaria elimination if submicroscopic gametocytes are included. Conclusions/Significance It will be very important to complement current methods of surveillance with enhanced diagnostic techniques to detect asexual parasites and gametocytes to more accurately plan, monitor and guide malaria control programs aimed at eliminating malaria.

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A Sub-Microscopic Gametocyte Reservoir Can Sustain Malaria Transmission

et al. (2011) A Sub-Microscopic Gametocyte Reservoir Can Sustain Malaria Transmission. PLoS ONE 6(6): e20805. doi:10.1371/journal.pone.0020805 A Sub-Microscopic Gametocyte Reservoir Can Sustain Malaria Transmission Stephan Karl 0 David Gurarie 0 Peter A. Zimmerman 0 Charles H. King 0 Tim G. St. Pierre 0 Timothy M. E. 0 Steffen Borrmann, Kenya Medical Research Institute - Wellcome Trust Research Programme, Kenya 0 1 School of Physics, The University of Western Australia , Crawley, Western Australia , Australia , 2 Department of Mathematics, Case Western Reserve University , Cleveland , Ohio, United States of America, 3 The Center for Global Health and Diseases, Case Western Reserve University , Cleveland , Ohio, United States of America, 4 School of Medicine and Pharmacology, The University of Western Australia, Fremantle Hospital , Western Australia , Australia Background: Novel diagnostic tools, including PCR and high field gradient magnetic fractionation (HFGMF), have improved detection of asexual Plasmodium falciparum parasites and especially infectious gametocytes in human blood. These techniques indicate a significant number of people carry gametocyte densities that fall below the conventional threshold of detection achieved by standard light microscopy (LM). Methodology/Principal Findings: To determine how low-level gametocytemia may affect transmission in present largescale efforts for P. falciparum control in endemic areas, we developed a refinement of the classical Ross-Macdonald model of malaria transmission by introducing multiple infective compartments to model the potential impact of highly prevalent, low gametocytaemic reservoirs in the population. Models were calibrated using field-based data and several numerical experiments were conducted to assess the effect of high and low gametocytemia on P. falciparum transmission and control. Special consideration was given to the impact of long-lasting insecticide-treated bed nets (LLIN), presently considered the most efficient way to prevent transmission, and particularly LLIN coverage similar to goals targeted by the Roll Back Malaria and Global Fund malaria control campaigns. Our analyses indicate that models which include only moderate-to-high gametocytemia (detectable by LM) predict finite eradication times after LLIN introduction. Models that include a low gametocytemia reservoir (requiring PCR or HFGMF detection) predict much more stable, persistent transmission. Our modeled outcomes result in significantly different estimates for the level and duration of control needed to achieve malaria elimination if submicroscopic gametocytes are included. Conclusions/Significance: It will be very important to complement current methods of surveillance with enhanced diagnostic techniques to detect asexual parasites and gametocytes to more accurately plan, monitor and guide malaria control programs aimed at eliminating malaria. - Funding: This work was supported by National Institutes of Health Research Grants R01TW008067 (CHK) and R01TW007872 (PAZ), funded by the Ecology of Infectious Diseases Program of the Fogarty International Center. TD was supported by a National Health and Medical Research Council Practitioner Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Recent regional roll back of malaria from Zanzibar, Eritrea, Ethiopia and Rwanda has been achieved by up-scaled and improved malaria control efforts through distribution of long lasting insecticide treated bed nets (LLIN) and effective treatment with artemisinin combination therapy (ACT) [13]. These successes plant new hope for malaria elimination given necessary levels of support [4]. In the progress report of the UN SecretaryGenerals Special Envoy for Malaria from 2009, it was announced that the continent of Africa now had surpassed average LLIN coverage of 40% with numerous African nations exceeding 60% [5]. In the malaria-endemic Southwest Pacific region, LLIN coverage rates of 70% have been reported from Papua New Guinea (PNG) and the Solomon Islands [6]. The importance of continued surveillance of progress towards the goal of near zero preventable deaths from malaria by 2015 has been stressed [5]. However for successful economic and strategic planning of largescale malaria control, it is essential to be able to predict how long an intensified malaria control effort will have to be sustained before the threat of resurgent malaria transmission is removed. Mathematical approaches, mainly based on fundamental work by Ross [7] and Macdonald [8], have been used to model malaria transmission and to predict the impact of malaria control during the malaria elimination campaigns in the 20th century [9]. These models utilize a population-based methodology whereby the relevant human population is divided into several subpopul (...truncated)


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Stephan Karl, David Gurarie, Peter A. Zimmerman, Charles H. King, Tim G. St. Pierre, Timothy M. E. Davis. A Sub-Microscopic Gametocyte Reservoir Can Sustain Malaria Transmission, PLOS ONE, 2011, Volume 6, Issue 6, DOI: 10.1371/journal.pone.0020805