Research Article: Risk Maps of Lassa Fever in West Africa

Date Published: March 3, 2009

Publisher: Public Library of Science

Author(s): Elisabeth Fichet-Calvet, David John Rogers, Robert Tesh

Abstract: BackgroundLassa fever is caused by a viral haemorrhagic arenavirus that affects two to three million people in West Africa, causing a mortality of between 5,000 and 10,000 each year. The natural reservoir of Lassa virus is the multi-mammate rat Mastomys natalensis, which lives in houses and surrounding fields. With the aim of gaining more information to control this disease, we here carry out a spatial analysis of Lassa fever data from human cases and infected rodent hosts covering the period 1965–2007. Information on contemporary environmental conditions (temperature, rainfall, vegetation) was derived from NASA Terra MODIS satellite sensor data and other sources and for elevation from the GTOPO30 surface for the region from Senegal to the Congo. All multi-temporal data were analysed using temporal Fourier techniques to generate images of means, amplitudes and phases which were used as the predictor variables in the models. In addition, meteorological rainfall data collected between 1951 and 1989 were used to generate a synoptic rainfall surface for the same region.Methodology/Principal FindingsThree different analyses (models) are presented, one superimposing Lassa fever outbreaks on the mean rainfall surface (Model 1) and the other two using non-linear discriminant analytical techniques. Model 2 selected variables in a step-wise inclusive fashion, and Model 3 used an information-theoretic approach in which many different random combinations of 10 variables were fitted to the Lassa fever data. Three combinations of absence∶presence clusters were used in each of Models 2 and 3, the 2 absence∶1 presence cluster combination giving what appeared to be the best result. Model 1 showed that the recorded outbreaks of Lassa fever in human populations occurred in zones receiving between 1,500 and 3,000 mm rainfall annually. Rainfall, and to a much lesser extent temperature variables, were most strongly selected in both Models 2 and 3, and neither vegetation nor altitude seemed particularly important. Both Models 2 and 3 produced mean kappa values in excess of 0.91 (Model 2) or 0.86 (Model 3), making them ‘Excellent’.Conclusion/SignificanceThe Lassa fever areas predicted by the models cover approximately 80% of each of Sierra Leone and Liberia, 50% of Guinea, 40% of Nigeria, 30% of each of Côte d’Ivoire, Togo and Benin, and 10% of Ghana.

Partial Text: Lassa fever (LF) is a viral haemorrhagic fever the pathogenic agent of which is an arenavirus Lassa virus (LASV) first discovered in 1969 in Nigeria, in a missionary nurse living in Lassa, a village close to the border with Cameroon [1]. Lassa fever is widespread in West Africa, affecting 2 million persons per annum with 5,000–10,000 fatalities annually [2]. Since its initial discovery, nosocomial outbreaks of Lassa fever have occurred repeatedly in Sierra Leone: Panguma, Kenema, 1971–83, 1997, Liberia: Zorzor, 1972; Phebe 1972, 1977, 1982; Ganta 1977, 1982 and Nigeria: Jos, 1970, 1993; Onitsha, 1974; Zonkwa, 1975; Vom, 1975–77, Imo, 1989; Lafia, 1993; and Irrua, 2004 [3],[4],[5],[6],[7],[8],[9]. In Guinea, some acute but isolated cases were recorded in hospitals [10] and a single rural outbreak was recorded on the Sierra Leone border in 1982–83 [11]. Between these two areas, namely in Côte d’Ivoire, Ghana, Togo and Benin, no outbreak has ever been recorded, though isolated cases show evidence of viral circulation in that area [12],[13],[14]. Lassa fever therefore appears to have 2 geographically separate endemic areas: the Mano River region (Guinea, Sierra Leone, Liberia) in the West, and Nigeria in the East.

The question that comes immediately to mind is: why does Lassa fever occur only in West Africa, whereas the range of its vertebrate host extends into East and Southern Africa? This is a recurrent question for other rodent-borne diseases (such as plague and hemorrhagic fevers with renal or pulmonary syndrome; see [42] for a review), which are also much more restricted in their distributions than are their hosts. Our analyses here show quite clearly that Lassa fever requires a particular combination of high (but not the highest) rainfall, and with a particular form of variability and seasonal timing, whereas its hosts can and do occur over regions experiencing a much wider range of rainfall conditions. Temperature appears to be less important in determining LASV distribution, although there are large differences between different areas; for example the annual mean and maxima in high risk areas are 27°C and 32°C respectively, whereas in low risk areas the mean temperature was approx. 38°C. Such high temperatures are known to increase LASV decay [43]. One curious feature of the present results is the seeming unimportance of vegetation variables in the predictor data sets. This lack of importance is not due to their strong correlation with rainfall variables (such a correlation might exclude them in step-wise inclusive variable selection), because Model 3 (using a method that avoids the problems of step-wise methods) independently and quite categorically failed to identify vegetation variables as important in determining LASV distribution. Taken together these results suggest that the survival of the virus outside of the vertebrate host might be a key to determining its distribution, and that this survival depends upon moisture or rainfall conditions above more or less all other environmental variables. This result differs from the conditions favouring other viral transmission; for example, low relative humidity and temperature favour avian influenza [44]. In the case of Lassa, the virus appears to survive better in humid conditions, during the rainy season. Rodents will be more often contaminated during their frequent movements at this season, for mating or dispersing into the surrounding fields [45]. Conversely, viral aerosol stability, seems to be higher when the humidity is lower [43], a condition that obviously occurs more frequently in the dry season. The experiments of Stephenson help to explain the numerous LF cases recorded in hospitals during the late dry season, between January and March in Sierra Leone and Nigeria ([46], Omilabu, pers. com.) but they do not necessarily throw much or any light on the persistence of Lassa fever in the general environment. We suggest that rainfall, within defined limits, is the single most important abiotic determinant of this persistence.



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