Defining disease heterogeneity to guide the empirical treatment of febrile illness in resource poor settings.

Paul N. Newton,Rapeephan R. Maude,Nicholas P. J. Day,Richard J. Maude,Roly D. Gosling,Mayfong Mayxay,Lisa J. White,Wirichada Pan-ngum,Jessica R. Fried

doi:10.1371/journal.pone.0044545

Abstract

BackgroundMalaria incidence is in decline in many parts of SE Asia leading to a decreasing proportion of febrile illness that is attributable to malaria. However in the absence of rapid, affordable and accurate diagnostic tests, the non-malaria causes of these illnesses cannot be reliably identified. Studies on the aetiology of febrile illness have indicated that the causes are likely to vary by geographical location within countries (i.e. be spatially heterogeneous) and that national empirical treatment policies based on the aetiology measured in a single location could lead to inappropriate treatment.MethodsUsing data from Vientiane as a reference for the incidence of major febrile illnesses in the Lao People's Democratic Republic (Laos) and estimated incidences, plausible incidence in other Lao provinces were generated using a mathematical model for a range of national and local scale variations. For a range of treatment protocols, the mean number of appropriate treatments was predicted and the potential impact of a spatially explicit national empirical treatment protocol assessed.FindingsThe model predicted a negative correlation between number of appropriate treatments and the level of spatial heterogeneity. A spatially explicit national treatment protocol was predicted to increase the number of appropriate treatments by 50% for intermediate levels of spatial heterogeneity.ConclusionsThe results suggest that given even only moderate spatial variation, a spatially explicit treatment algorithm will result in a significant improvement in the outcome of undifferentiated fevers in Laos and other similar resource poor settings.

Highlights

The results suggest that given even only moderate spatial variation, a spatially explicit treatment algorithm will result in a significant improvement in the outcome of undifferentiated fevers in Lao People’s Democratic Republic (Laos) and other similar resource poor settings
As malaria incidence declines in parts of SE Asia, an increasingly recognised important problem is how to treat patients presenting with non-malaria febrile illness
In a study in France, the national empirical treatment protocol for the treatment of respiratory infections was demonstrated to be appropriate [5], whereas in rural India misdiagnosis of malaria was common, leading to frequent inappropriate treatments (i.e. 40% of non-malarial acute undifferentiated fever cases testing negative for malaria by RDT were treated with antimalarials) [4]

Summary

Introduction

As malaria incidence declines in parts of SE Asia, an increasingly recognised important problem is how to treat patients presenting with non-malaria febrile illness. Where the cause of particular non-malaria febrile illness is not identified using diagnostic tests, an empirical treatment protocol is deployed. In a study in France, the national empirical treatment protocol for the treatment of respiratory infections (published by Societe de Pathologie Infectieuse de Langue Francaise [6]) was demonstrated to be appropriate [5], whereas in rural India misdiagnosis of malaria was common, leading to frequent inappropriate treatments (i.e. 40% of non-malarial acute undifferentiated fever cases testing negative for malaria by RDT were treated with antimalarials) [4]. Studies on the aetiology of febrile illness have indicated that the causes are likely to vary by geographical location within countries (i.e. be spatially heterogeneous) and that national empirical treatment policies based on the aetiology measured in a single location could lead to inappropriate treatment

Methods

Results

Conclusion