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Community screening and treatment of asymptomatic carriers of Plasmodium falciparum with artemether-lumefantrine to reduce malaria disease burden: a modelling and simulation analysis

Steven E Kern19*, Alfred B Tiono2, Michael Makanga3, Adama Dodji Gbadoé4, Zulfiqarali Premji5, Oumar Gaye6, Issaka Sagara7, David Ubben8, Marc Cousin9, Fiyinfolu Oladiran10, Oliver Sander9 and Bernhards Ogutu1112

Author Affiliations

1 Department of Pharmaceutics, University of Utah, Salt Lake City, Utah, USA

2 Public Health Department, Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou, Burkina Faso

3 European and Developing Countries Clinical Trials Partnership (EDCTP), Cape Town, South Africa

4 Department of Paediatrics, University of Lomé, Lomé, Togo

5 Department of Parasitology and Medical Entomology, Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania

6 Faculty of Medicine, University Cheikh Anta Diop of Dakar (CAD), Dakar, Senegal

7 Malaria Research and Training Center, University of Bamako, Bamako, Mali

8 Medicines for Malaria Venture, Geneva, Switzerland

9 Novartis Pharma, Basel, Switzerland

10 Novartis South Africa, Johannesburg, South Africa

11 Centre for Clinical Research, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya

12 Malaria Clinical Trials Alliance - INDEPTH Network, Nairobi, Kenya

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Malaria Journal 2011, 10:210  doi:10.1186/1475-2875-10-210

Published: 29 July 2011

Abstract

Background

Asymptomatic carriers of Plasmodium falciparum serve as a reservoir of parasites for malaria transmission. Identification and treatment of asymptomatic carriers within a region may reduce the parasite reservoir and influence malaria transmission in that area.

Methods

Using computer simulation, this analysis explored the impact of community screening campaigns (CSC) followed by systematic treatment of P. falciparum asymptomatic carriers (AC) with artemether-lumefantrine (AL) on disease transmission. The model created by Okell et al (originally designed to explore the impact of the introduction of treatment with artemisinin-based combination therapy on malaria endemicity) was modified to represent CSC and treatment of AC with AL, with the addition of malaria vector seasonality. The age grouping, relative distribution of age in a region, and degree of heterogeneity in disease transmission were maintained. The number and frequency of CSC and their relative timing were explored in terms of their effect on malaria incidence. A sensitivity analysis was conducted to determine the factors with the greatest impact on the model predictions.

Results

The simulation showed that the intervention that had the largest effect was performed in an area with high endemicity (entomological inoculation rate, EIR > 200); however, the rate of infection returned to its normal level in the subsequent year, unless the intervention was repeated. In areas with low disease burden (EIR < 10), the reduction was sustained for over three years after a single intervention. Three CSC scheduled in close succession (monthly intervals) at the start of the dry season had the greatest impact on the success of the intervention.

Conclusions

Community screening and treatment of asymptomatic carriers with AL may reduce malaria transmission significantly. The initial level of disease intensity has the greatest impact on the potential magnitude and duration of malaria reduction. When combined with other interventions (e.g. long-lasting insecticide-treated nets, rapid diagnostic tests, prompt diagnosis and treatment, and, where appropriate, indoor residual spraying) the effect of this intervention can be sustained for many years, and it could become a tool to accelerate the reduction in transmission intensity to pre-elimination levels. Repeated interventions at least every other year may help to prolong the effect. The use of an effective diagnostic tool and a highly effective ACT, such as AL, is also vital. The modelling supports the evaluation of this approach in a prospective clinical trial to reduce the pool of infective vectors for malaria transmission in an area with marked seasonality.