NDT Advance Access originally published online on December 16, 2005
Nephrology Dialysis Transplantation 2006 21(3):826-827; doi:10.1093/ndt/gfi334
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First evidence of fatal hantavirus nephropathy in India, mimicking leptospirosis
Clinical and Epidemiological Virology and Rega Institute for Medical Research University of Leuven Leuven, Belgium
Email: jan.clement{at}uz.kuleuven.ac.be
Sir,
In a recent Indian serosurvey [1], it was announced that ‘no reports of hantavirus infections in humans from India existed [before 2005]’. We wish to point out that serological and clinical evidence of hantavirus infection in India was already well documented before 2005.
From 1998 on, we screened leptospirosis-suspected cases in India for the only known cosmopolitan hantavirus serotype, Seoul virus (SEOV). Wild rats are the reservoir of SEOV and these commensal rodents have a documented presence worldwide [2], including India. SEOV can cause thrombocytopenia with concomitant kidney and liver involvement, thus, mimicking leptospirosis [2]. In addition to murine SEOV, we have a policy to use also an arvicoline screening antigen, i.e. from Puumala virus (PUUV). PUUV is spread in Europe and Russia by bank voles, causing a milder form of nephropathy with thrombocytopenia, called ‘nephropathia epidemica’ (NE). This simple dual approach of screening leptospirosis-suspected sera enabled us to document in 1992 the first serologically confirmed hantavirus cases in the New World (Recife, Brazil) [3], as well as in the Netherlands [4] and in Northern Ireland [5].
In short, we detected hantavirus-specific immunoglobulin (Ig) G and IgM antibodies by strip immunoblot assay (SIA) layered with SEOV and PUUV recombinant nucleoproteins (rNP) (courtesy of Brian Hjelle, University of New Mexico) and by PUUV rNP enzyme-linked immunosorbent assay (ELISA). All studied sera had to be seronegative for leptospirosis in micro-aggluntination test (MAT) testing in India, and negative again in our hands with a specific and probably more sensitive Patoc–IgG and –IgM ELISA test. Dengue infection was likewise serologically excluded by immunochromatography.
In a first 1998–1999 serosurvey, we found evidence of SEOV-like and/or PUVV-like antibodies [6]. Up to 2000, however, no clinically documented hantavirus cases had been reported from India. Therefore, we started a prospective study in the Chennai and Cochin area in southern India, investigating leptospirosis-suspected but MAT- and Patoc ELISA-negative cases. We detected 7/60 (12%) positives for SEOV in IgG SIA, i.e. showing a higher band intensity for SEOV than for PUUV, and 3/60 (5%) PUUV-positives. All IgG SIA-positives, except one SEOV + serum, were also IgM SIA-positive, thus, confirming for the first time recent hantavirus infections in at least nine Indian cases [7]. Two cases were fatal: one in Chennai and one in Cochin. Both patients had developed dialysis-requiring acute renal failure with severe hypoxia.
Thottapalayam virus (TPMV) is the only indigenous hantavirus documented so far in India, being isolated in 1964 from a shrew near Vellore in Southern India [7]. To date, no human pathogenicity for TPMV has been shown [7], but it is noticeable that shrews are insectivores, not rodents. So far, human hantavirus pathogenicity has been linked to rodents only [2]. Although we found evidence of a SEOV-like infection in 12% of the Indian ‘leptospirosis-like’ cases, another 5%, with all the more severe cases, looked surprisingly like PUUV infections. However, the worldwide geographical repartition of hantaviruses is well defined by a close co-evolution with their respective rodent carriers [2]. But the bank vole is absent from the Indian biotope and, consequently, PUUV should also be absent or spread eventually by another arvicoline, as yet unidentified, rodent. We prefer to believe, however, that our positive PUUV (and SEOV?) results may be cross-reactions with TPMV or yet another unknown hantavirus in India. Thus, the low yield of our screening may be explained by the fact that only, or in part, cross-reacting antigens were used. Finally, severe clinical courses as depicted above are atypical for the mostly milder NE. In fact, the fatal outcome of the Cochin case is rather reminiscent of (South-) American forms of the so-called ‘hantavirus (cardio-) pulmonary syndrome’ (HPS). However, HPS can exceptionally also occur in Old World PUUV cases [8].
To elucidate this problem, we are now in the process of confirming our results using the polymerase chain reaction and with neutralization tests on the largest possible battery of known hantaviruses, preferably also including TPMV. Without this gold standard for hantavirus serology [2], no final decision can be made about the exact nature and importance of hantaviruses in India.
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Acknowledgments |
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We wish to thank Prof. W. Terpstra and Dr R. Hartskeerl of the Tropical Institute of Biomedical Research, Amsterdam, the Netherlands, for their help in providing us with the Indian sera.
Conflict of interest statement. None declared.
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 Top References |
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- Chandy S, Mitra S, Sathish N et al. A pilot study for serological evidence of hantavirus infection in human population in south India. Indian J Med Res 2005; 122: 211–215[Medline]
- Clement J, Heyman P, McKenna P et al. The hantaviruses of Europe: from the bedside to the bench. Emerg Infect Dis 1997; 3: 205–211[Medline]
- Hinrichsen S, Medeiros de Andrade A, Clement J et al. Evidence of hantavirus infection in Brazilian patients from Recife with suspected leptospirosis. Lancet 1993; 341: 50[Medline]
- Osterhaus ADME, Groen J, UytdeHaag FGCM et al. Hantavirus nephropathy in the Netherlands. Lancet 1989; 2: 338–339[Medline]
- McKenna P, Clement J, Matthys P et al. Serological evidence of hantavirus disease in Northern Ireland. J Med Virol 1994; 43: 33–38[Medline]
- Clement J, Hinrichsen S, Crescente J et al. Hantavirus-induced hemorrhagic fever with renal syndrome (HFRS) has to be considered in the differential diagnosis of leptospirosis-suspected cases in the New and the Old World. Am J Trop Med Hyg 1999; 61: 316–317
- Clement J, Muthusethupathi M, Nainan G, van Ranst M. First fatal cases of hantavirus nephropathy in India. Clin Inf Dis 2000; 31: 315
- Clement J, Colson P, McKenna P. Hantavirus pulmonary syndrome in New England and Europe. N Engl J Med 1994; 331: 545–548
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