Re: Gujarat Leptospirosis 2013 - 6 deaths due to undiagnosed illness?
Leptospirosis? Or plague? Or hantavirus?
Published Date: 2013-10-14 15:00:44
Subject: PRO/AH/EDR> Undiagnosed deaths - India (02): (GJ) comments
Archive Number: 20131014.2000971
UNDIAGNOSED DEATHS - INDIA (02): (GUJARAT) COMMENTS
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[1]
Date: Sat 12 Oct 2013 Oct 2013
From: T Jacob John <tjacobjohn@yahoo.co.in> [edited]
Comment on the undiagnosed deaths in Surat
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In October 1994 there was panic, pandemonium, and enormous out-migration after Surat city (Gujarat State) was declared affected with an outbreak of pneumonic plague. The picture was that of adults, not old, mostly men, developing fever, blood in sputum, and high case-fatality. My guess is that the present situation is reminiscent of that old scary experience and the present anxiety is understandable against this background.
Pneumonic plague is easily diagnosed in a bacteriology laboratory with readily available clinical specimen by way of sputum and commonly used culture media. Although not mentioned in the report, plague would have been excluded before specimens are dispatched to the National Institute of Virology (NIV) in Pune (in Maharashtra State). Moreover, Crimean-Congo hemorrhagic fever has been reported in recent years in Ahmedabad (also in Gujarat State) and that was diagnosed by NIV.
The report does not say how leptospirosis was excluded but I wonder if that is the real case. Post-floods leptospirosis is very likely to occur and pulmonary hemorrhagic leptospirosis has been reported previously in 1994 in Surat and in nearby Valsad. Diagnosis of leptospirosis is not easy -- most laboratories rely on serological (antibody) tests -- and we need more details before concluding that the disease is not leptospirosis.
--
T Jacob John
Former (Retired) Professor of Clinical Microbiology and Clinical Virology
Christian Medical College,
Vellore, Tamil Nadu
India
<tjacobjohn@yahoo.co.in>
[ProMED-mail thanks Professor T Jacob John for his prompt response to the ProMED-mail request for information. His recollection of an outbreak of pneumonic plague with similar characteristics in Surat city in 1994 is intriguing and certainly worthy of further investigation. Until results become available from the National Institute of Virology it is too early to attribute the outbreak to viral infection. As Professor John concludes, leptospirosis remains a possibility and further diagnostic testing should be undertaken. - Mod.CP]
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[2]
Date: Sun 13 Oct 2013
From: Jan Clement <jan.clement.dr@telenet.be> [edited]
Possible involvement of hantavirus fever in the Surat outbreak
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In summary, and despite insufficient information so far, a hitherto unknown but sometimes fatal viral hemorrhagic fever (VHF), first suspected of being leptospirosis, seems to have spread in the Surat (Gujarat state) region, after heavy local floods. Several points of interest may help the local health authorities and the National Institute of Virology (NIV) in Pune to elucidate this mysterious illness:
1. Hantavirus fever (HTVF), and particularly the so-called "hemorrhagic fever with renal syndrome" (HFRS) form is the great imitator of leptospirosis in virtually every aspect: clinics, lab anomalies, most anatomo-pathological findings (including kidney biopsies), and even most epidemiological aspects. HTVF (worldwide an estimated 150 000 cases/year) is after leptospirosis (worldwide an estimated 200 000 cases/year) the most globally spread zoonosis, and both are mainly rodent-borne (Clement J, Maes P, Van Ranst M: Acute kidney injury in emerging, non-tropical infections. Acta Clin Belg 2007; 62(6): 387-95).
2. The rodent-borne origin explains why both diseases can occur, often even concomitantly, after local floods: rats, or other rodent carriers of pathogenic hantaviruses, fleeing from the water, often take refuge in human habitats. The 1st serologically confirmed cases of HTVF in the New World were documented in Recife (Brazil), after heavy floods (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). In Europe, the most important hantaviral pathogen is Puumala virus (PUUV), carried by the bank vole (_Myodes glareolus_), and causing often dense local outbreaks of HTVF, aptly called "nephropathia epidemica" (NE). The 1st Franco-Belgian NE outbreak was documented in 1993, after heavy rains causing floods of the local river Meuse in both countries (Clement J, Mc Kenna P, Colson P, et al: Hantavirus epidemic in Europe. Lancet 1994; 343(8889): 114-6. doi:10.1016/S0140-6736(94)90841-9).
3. All forms of HTVF, and even the New World forms of so-called "hantavirus pulmonary syndrome" (HPS), have also a clear RENAL involvement, that is earlier, cheaper, and easier to detect than its pulmonary counterpart (Clement J, Maes P, Lagrou K, et al: A unifying hypothesis and a single name for a complex globally emerging infection: hantavirus disease. Eur J Clin Microbiol Infect Dis 2012; 31(1): 1-5. doi: 10.1007/s10096-011-1456-y). Whereas so-called acute kidney injury (AKI) still needs a serum creatinine dosage for confirmation, initial and frequently massive (nephrotic-range) proteinuria is often present prior to AKI, but can be very transient, often disappearing within 2 to 3 weeks. Such a + to +++ dipstick degree of initial proteinuria can be performed as a bed-side test everywhere, even in resource-poor regions. If positive, this finding can exclude practically from the start other similar infections occurring in outbreaks such as plague, tularemia, rickettsioses, and even leptospirosis, since in the latter, nephrotic-range proteinuria is never present.
4. Vomiting of blood is an unusual sign of HTVF, but this symptom is not exclusive, since HTVF is and remains the only VHF present throughout the Northern Hemisphere. Moreover, some "newer" hantaviral strains, such as the different subspecies of Dobrava virus (DOBV), are characterized by hemorrhagic complications, which can be life-threatening.
5. Whereas it is clear that the wild rat-transmitted Seoul virus (SEOV) is present in India (but no human SEOV nephropathy has been documented so far), the 1st 2 fatal, and some non-fatal HTVF cases, have been demonstrated in India to be serologically related to PUUV (Clement J, Maes P, Muthusethupathi M, et al: First evidence of fatal hantavirus nephropathy in India, mimicking leptospirosis. Nephrol Dial Transpl 2006; 21(3): 826-7
http://ndt.oxfordjournals.org/cgi/content/full/21/3/826?etoc). This should be interpreted as a cross-reaction, since PUUV is absent in India, given the total absence of its carrier _Myodes glareolus_. However, the 2 fatal Indian cases had both renal and pulmonary involvement, and both died in shock, a combination reminiscent of the American HPS infection, still bearing a 35 percent fatality rate, even in tertiary care centres. It should be remembered that in the USA, a country where up to 1993, HTVF was (incorrectly) considered as being absent, the 1st step in unravelling the mystery of the reputed 1993 HPS outbreak, was a similar serological cross-reaction with PUUV (Jonsson CB, Figueiredo LT, Vapalahti O: A global perspective on hantavirus ecology, epidemiology, and disease. Clin Microbiol Rev 2010; 23(2): 412-41
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2863364/). Since all American HPS-inducing hantaviruses are genetically more closely related to PUUV than to any other hantaviral pathogen, PUUV cross-reactions in severe HFRS + HPS cases may point to a hitherto unknown Indian hantavirus, with a hitherto unknown rodent (or insectivore?) reservoir.
6. Finally, in a prospective study of cases with AKI and fever, hospitalized in Sri-Lanka, a country highly endemic for leptospirosis, serological evidence was found for sympatric occurrence of SEOV and PUUV. Sri-Lanka has exactly the same small mammal fauna as neighbouring India, suggesting that a PUUV-like agent is probably spread by the same carrier in the 2 countries. Moreover and more importantly, for the 1st time concomitant presence of both leptospirosis and hantavirus was demonstrated in some more severe cases, meaning that even a lab confirmation of (well-known) leptospirosis, does not automatically exclude concomitant (but underestimated) HTVF. (Sunil-Chandra NP, Clement J, Maes P, et al: A new hantaviral pathogen in Sri-Lanka. Proceedings of the European Society for Clinical Virology, Annual Meeting Saariselka, Finland, 12-15 Mar 2008. Abstract P8-10, p. 46).
--
Clement J MD, Maes P Ph D, & Marc Van Ranst MD, PhD
National Belgian Reference Laboratory for Hantavirus Infections,
Clinical Virology,
University Hospital Gasthuisberg
University of Leuven
Leuven
Belgium
<jan.clement.dr@telenet.be>
[ProMED-mail thanks Dr Clement and colleagues for this carefully argued statement in favour of the involvement of hantavirus infection in the hemorrhagic fever cases reported from the city of Surat in Gujarat state, India.
As commented above in part 1, the results of the analysis of clinical samples at the Indian National Institute of Virology in Pune (Maharashtra) are awaited. - Mod.CP
