Smoking and other risk factors for hantavirus infections: the whole story

To the Editor: We read with great interest the recent case-control study by Vapalahti et al. [1] on risk factors for nephropathia epidemica (NE). In their article, the authors describe ‘smoking as the most striking and clear risk factor’. This interesting finding came as no surprise, since NE is actually caused by inhalation of aerosolized PUUV particles, leading to an acute viral illness with possible lung symptoms which may be predominant, even in Europe [2]. Smoking may also increase the risk of ingestion of rodent faeces or urine through poor hand hygiene. Nevertheless, PUUV and all other pathogenic hantaviruses worldwide are almost never listed as ‘respiratory viruses’, although these emerging infections, and particularly the New World variants, have caused more casualties so far than two other emerging respiratory pathogens, SARS and avian influenza [3]. However, the authors omitted to mention that smoking had already been reported as a major risk factor more than 11 years ago in the earliest European case-control study on NE, completed after the first major NE peak in 1993 in Belgium [4]. In this admittedly much smaller study, 41 seroconfirmed NE cases were compared to 37 seronegative household controls and 32 seronegative neighbourhood controls. This omission is all the more remarkable, since the Belgian study is included by the Finnish authors in their list of references. Smoking and several other striking points of resemblance between their study and the Belgian study are not, however, mentioned, including similarity of the mean age of the NE cases (46 years vs. 44 years), absence of children <15 years in both studies, predominance of males in the study group but of females in the control group, use of matched pairs with seronegative controls living in the neighbourhood, a majority of cases living in a one-family house, and in a rural (often forested) area, etc. As suggested by the Finnish authors in their last paragraph, similar studies have the great merit of corroborating each other if very similar outcomes are reached, and should consequently be highlighted, rather than ignored. Indeed, smoking emerged as the second most important risk factor for NE in the Belgian study, with an odds ratio (OR) of 9.1 (95% CI 3.2–25.9, P=0.01) for cases vs. controls. To rule out confounding factors for similar living conditions among family controls, a comparison was made with neighbouring controls only, but resulted in an even higher OR of 9.8 (95% CI 2.6–36.6, P=0.01). Conditional logistic regression of the matched pairs (exactly as in the Finnish study) yielded again an unchanged OR of 9.1 (95% CI 2.6–31.2) of yet higher significance (P=0.0004), second only to the risk factor wood-cutting, with OR 15.5 (95% CI 2.0–119.6, P=0.008) [4]. These results support the intriguing Finnish hypothesis that the condition of the human airways, altered by chronic smoking, might facilitate the uptake of aerosolized hantaviruses. If so, then the mean number of smoked cigarettes per day should give an even better indication, a factor not examined, however, in this study. In contrast, the Belgian study showed that NE cases smoked significantly more than controls [4]. ‘Type of housing’ and ‘ living environment’ were described in the Finnish study as having strong correlations, as expected. The dominant biotope in Finland is the boreal coniferous forest or taiga, in contrast to the deciduous broad-leaf forests in Western Europe. However, the PUUV reservoir in both regions is a rodent from the family Cricetidae, the bank vole or Myodes glareolus, a common small mammal in both forest biotopes [5]. So, the strongest risk factor linked to housing and/or living environment might be in fact the distance of the human habitat or working place to the forest, an element Epidemiol. Infect. (2011), 139, 1284–1286. f Cambridge University Press 2010