Abstract
Leptospirosis and haemorrhagic fever with renal syndrome (HFRS) are hard to distinguish clinically since these two important rodent-borne zoonoses share hallmark symptoms such as renal failure and haemorrhage. Leptospirosis is caused by infection with a spirochete while HFRS is the result of an infection with certain hantaviruses. Both diseases are relatively rare in the Netherlands. Increased incidence of HFRS has been observed since 2007 in countries that border the Netherlands. Since a similar rise in incidence has not been registered in the Netherlands, we hypothesise that due to overlapping clinical manifestations, hantavirus infections may be confused with leptospirosis, leading to underdiagnosis. Therefore, we tested a cohort of non-travelling Dutch patients with symptoms compatible with leptospirosis, but with a negative diagnosis, during 2010 and from April to November 2011. Sera were screened with pan-hantavirus IgG and IgM enzyme-linked immunosorbent assays (ELISAs). Sera with IgM reactivity were tested by immunofluorescence assay (IFA). ELISA (IgM positive) and IFA results were confirmed using focus reduction neutralisation tests (FRNTs). We found hantavirus-specific IgG and/or IgM antibodies in 4.3% (11/255) of samples taken in 2010 and in 4.1% (6/146) of the samples during the 2011 period. After FRNT confirmation, seven patients were classed as having acute Puumala virus infections. A review of hantavirus diagnostic requests revealed that at least three of the seven confirmed acute cases as well as seven probable acute cases of hantavirus infection were missed in the Netherlands during the study period.
Highlights
Hantaviruses, negative-stranded RNA viruses belonging to the Bunyaviridae family, can cause severe disease in humans
A sample was deemed to be negative for leptospirosis if the patient did not meet the case definition for leptospirosis – i.e. the inhouse enzyme-linked immunosorbent assays (ELISAs) for leptospirosis was below the cut-off titre of 1:80 and the microscopic agglutination test (MAT) showed no relevant titre of Leptospira-specfic antibodies (
Nine of the 27 IgM ELISAresponsive samples tested positive for both Puumala virus (PUUV) IgM and IgG by immunofluorescence assay (IFA)
Summary
Hantaviruses, negative-stranded RNA viruses belonging to the Bunyaviridae family, can cause severe disease in humans. Recent reports describe PUUV infections with a broader clinical spectrum, ranging from mild febrile cases, without renal impairment or haemorrhage, to severe respiratory manifestations without any signs of renal involvement [7,8]. The occurrence of PUUV infection in the Netherlands has been restricted to the eastern and southern parts of the country, with an incidence of 25–30 cases reported per year (approximately 0.04–0.18 cases per 100,000 population) [9]. Since 2007, several studies have described an increase in the number of human PUUV infections in neighbouring countries at the eastern (Germany) and southern borders (Belgium) [10,11,12]. A similar increase in the number of human PUUV infections has not been observed in the Netherlands
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