Inclusion Body Disease - An Update

INTRODUCTION

This disease was described many years ago (Schumacher et al, 1994; Chang and Jacobson, 2010; Axthelm, 1985) and is considered transmissible, progressive and fatal. It has been described all over the world including Australia, South America, United States and Europe. This disease is characterised by large intracytoplasmatic eosinophilic inclusions in neurons and epithelial cells in different organs (Schumachaer, 1994).

It has been well defined in Boidae and Pythonidae families (Schumacher et al, 1994; Jacobson et al, 2001; Wosniak et al, 2000; Pees et al, 2010; Vancraeynest et al, 2006; Raymond et al, 2001; Carlisle-Nowak et al, 1998). It was first described in 1970 in the United States in private collections and zoological centres (Schumacher et al, 1994), in Morelia spilota spilota and M. spilota variegata in Australia (Carlisle-Nowak, 1998), Boa constrictor in Spain and Belgium (Oros et al, 1998; Vancraeynest, 2006), Eunectes murinus, Eunectes notaeus, Epicrates cenchris, Epicrates striatus, Achranthophis madagascariensis, Python molurus molurus, Python molurus bivittatus (Schumacher et al, 1994), Python reticulatus, Python regius, Lampropeltis getula (Jacobson et al, 2007), Bothriechis marchi (Raymond et al, 2001) and Corallus hortulanus (Turchetti et al, 2013).

AETIOLOGY

Previous studies presumed involvement of a retrovirus (Jacobson et al, 2001; Schumacher et al, 1994), although endogenous retroviruses have been identified in Boa constrictor (Martin et al, 1997; Huder et al, 2002), proving difficult to relate virus and disease. A specific protein of 68kDa was purified from affected tissues verification on whether it was endogenous or viral lacked (Wozniak et al, 2000).

The causative agent has been a mystery for decades but recent studies have shown that an arenavirus could be the cause of many of the cases of inclusion body disease as two viruses were identified with characteristics attributable to arenavirus and with similarities to filovirus (Stenglein et al, 2012). In another study highly divergent arenavirus with similarities to Golden Gate Virus were found (Bodewes et al, 2013).

Arenaviridae are enveloped negative monocaternary RNA viruses with two genomic segments (Jankovich et al, 2010; King et al, 2011), with arenavirus as the only genre. Arenavirus had been solely identified previously in mammals with the capacity to cause disease in humans. They are responsible for diseases with zoonotic implications including Venezuelan Haemorrhagic Fever, Argentine haemorrhagic fever, Bolivian Haemorrhagic fever, Brazilian Haemorrhagic Fever, Lymphocytic coryomeningitis and Lassa Fever. There is no evidence to suggest that reptile arenavirus may cause disease in humans.

TRANSMISSION

Although there is no evidence to suggest transmissible disease, the exact mechanism is unknown (Schumacher et al, 1994). It has been proposed that snakes may become infected after ingesting rats or mice. Callithrid hepatitis virus  was shown to be identical to LCMV in rodents that were offered as food (Stephensen et al, 1991, 1995). The presence of the snake mite Ophionyssus natricis in affected colonies has suggested a possible vector implication (Chang, 2010). Other transmission routes could include direct, venereal or vertical.

CLINICAL SIGNS

These may vary and may include stomatitis, regurgitation, anorexia, lethargy, neurological signs (incoordination, disorientation, head tremors) and death. Other signs may include pneumonia, cutaneous sarcomas, lymphoproliferative disorders and leukaemia (Marschang, 2011).

Viral immunosupression and secondary infections are common and may present as recurring chronic stomatitis (personal observation). Asymptomatic animals, generally boas, with inclusion bodies in tissues also exist.

Clinical and hystological manifestations, along with disease progression may vary between boas and pythons (Chang and Jacobson, 2010; Axthelm, 1985; Schumacher et al, 1994). In pythons, the presence of inclusions in the central nervous system (CNS) along with with neurological signs seems to be the most common presentation. In boas they seem to be found in different tissues and may present with regurgitations. Pythons seem to succumb to the disease quicker than boas, and survival may be months to years with supportive care.

DIAGNOSIS

In live animals arenavirus detection through polymerase chain reaction (PCR) in circulating white blood cells, liver and tonsils biopsies is the current line of investigation here in Europe and tests are now available at a recognised laboratory.

Hystopathological staining with hematoxilin-eosin (H&E) will show eosinophilic inclusions in tissues. The inclusions are 68-KDa proteins which are now recognised as arenavirus nucleoproteins mainly found in CNS, although may also be found in oesophageal tonsils, respiratory epithelium, gastrointestinal epithelium, hepatocytes, pancreatic and renal tubular epithelial cells. Although the presence of these inclusions is diagnostic, their absence does not discard disease.

Wright-Giemsa or H&E stains may identify inclusions in lymphocytes (Pees et al, 2010) and other circulating blood cells, although a chronological scale of these inclusions in circulating blood is still unknown. A recommendation is to examine blood prior to tissue samples. 

Another diagnostic technique currently under investigation is inclusion isolation via hibridoma technology which renders mononuclear antibodies (MAB) anti-IBDP, staining tissue inclusions in paraffin. Immunohistochemistry post cytospin technique is also currently being validated.

TREATMENT AND PREVENTION

There is currently no specific treatment and euthanasia is recommended for those individuals where there is a transmission risk or presenting with neurological signs. Due to ongoing advances and research in understanding this disease and causative agent, we expect more studies and data in the near future.

A quarantine period of 90 days and up to 6 months for boas (EAZA) has been suggested, coupled with mite control.


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