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BackgroundThe importation of malaria to non-endemic countries remains a major cause of travel-related morbidity and a leading cause of travel-related hospitalizations. Currently they are three priority medications for malaria prophylaxis to West Africa: mefloquine, atovaquone/proguanil and doxycycline. We investigate the cost effectiveness of a partial reimbursement of the cheapest effective malaria chemoprophylaxis (mefloquine) for travellers to high risk areas of malaria transmission compared with the current situation of no reimbursement.MethodsThis study is a cost-effectiveness analysis based on malaria cases imported from West Africa to Switzerland from the perspective of the Swiss health system. We used a decision tree model and made a literature research on the components of travel related malaria. The main outcome measure was the cost effectiveness of malaria chemoprophylaxis reimbursement based on malaria and deaths averted.ResultsUsing a program where travellers would be reimbursed for 80% of the cost of the cheapest malaria chemoprophylaxis is dominant (i.e. cost saving and more effective than the current situation) using the assumption that currently 68.7% of travellers to West Africa use malaria chemoprophylaxis. If the current usage of malaria chemoprophylaxis would be higher, 82.4%, the incremental cost per malaria case averted is € 2'302. The incremental cost of malaria death averted is € 191'833.The most important factors influencing the model were: the proportion of travellers using malaria chemoprophylaxis, the probability of contracting malaria without malaria chemoprophylaxis, the cost of the mefloquine regimen, the decrease in the number of travellers without malaria chemoprophylaxis in the reimbursement strategy.ConclusionsThis study suggests that a reimbursement of 80% of the cost of the cheapest effective malaria chemoprophylaxis (mefloquine) for travellers from Switzerland to West Africa is highly effective in terms of malaria cases averted and is cost effective to the Swiss health system. These data are relevant to discussions about the cost effectiveness of malaria chemoprophylaxis reimbursement for vulnerable groups such as those visiting friends and relatives who have the highest risk of malaria, who are least likely to use chemoprophylaxis.

Cellular resistance to etoposide has been correlated both with reduced levels and an aberrant cytoplasmic accumulation of the drug`s target, topoisomerase IIα (topo IIα). It is not known, however, whether a cytoplasmic pool of topo IIα is sufficient to confer drug resistance on cultured mammalian cells. In our study, we have transfected mouse fibroblasts and human 293 cells with truncated forms of human topo IIα fused to GFP and have examined the transformants for the subcellular localization of topo IIα and their resistance to etoposide. Transient transfection resulted in high‐level expression of all GFP‐topo IIα fusions tested, whereas in stably transfected cells the levels varied significantly. Transfectants expressing a central or a carboxy‐terminal topo IIα domain (aa 428‐1504, 639‐1028 or 1028‐1504) accumulated high levels of the fusion proteins, while only very low amounts of GFP‐topo IIα proteins were observed in cell lines expressing constructs that retain the amino‐terminus of the enzyme (aa 1‐1214, aa 1‐939, aa 1‐611). Our results suggest that the topo IIα amino‐terminus affects the stability of truncated forms of the enzyme in mammalian cells, perhaps due to targeted degradation. Assays that screen for cell vitality and DNA synthesis reveal no significant changes in etoposide sensitivity in transfected cells expressing high levels of cytoplasmic or nuclear localized topo II fusion proteins. Retroviral expression of a cytoplasmically anchored domain of human topo IIα also failed to confer drug resistance. These results suggest that a cytoplasmic pool of topo IIα is not sufficient to render cultured mammalian cells drug resistant. Int. J. Cancer 88:99–107, 2000. © 2000 Wiley‐Liss, Inc.

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