key: cord-277181-rvjvuxor
authors: Liu, Chen-Hsuan; Hsu, Yung-Hsiang
title: The Role of Comparative Pathology in the Investigation of Zoonoses
date: 2007-09-30
journal: Tzu Chi Medical Journal
DOI: 10.1016/s1016-3190(10)60004-3
sha: 
doc_id: 277181
cord_uid: rvjvuxor

Abstract Emerging and re-emerging zoonoses have raised great concerns in both human and animal health worldwide in the past 20 years. Rudolph Virchow proposed a “one medicine” discipline and emphasized the importance of cooperation 150 years ago. In the face of emerging threats from unpredictable zoonoses, human medicine and veterinary medicine should not be separate and independent sciences. Anatomic pathologists who are capable of analyzing and interpreting anatomical manifestations of diseases to obtain a definite diagnosis or exclude a wide variety of diseases play an important role in the diagnostic team. Although disease-associated microbes are numerous, morphologic patterns of tissue reaction caused by microbes are limited. Therefore, the interactions between microbes and host determine the histological changes in the target tissues. The contributions of anatomic pathology, with its use of morphologic similarities and special techniques, are important in zoonosis diagnosis. This can be seen in retrospective case studies of recent zoonoses such as multinucleated syncytial giant cells in severe acute respiratory syndrome and mouse hepatitis virus infection, syncytial cells in Henipahvirus infection and paramyxovirus, neuronal vacuolation in bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease, and Streptococcus suis type 2 meningitis. In Taiwan, the Chinese Society for Comparative Pathology, which was established in 1994, provides for this interaction. Interlaboratory cooperation plays an important role in the diagnosis, surveillance, and control of emerging and re-emerging zoonoses.

Emerging and re-emerging diseases have had a devastating impact on both human and animal health worldwide in the past 20 years, and zoonotic diseases have raised particular attention (Table 1) . It is estimated that three-fourths of emerging diseases are zoonotic [1, 2] . Facing the invasion of so many unpredictable pathogens and the emergence of bioterrorism as a global threat, a fast and definite diagnosis has become more important to eradicate or control the spread of diseases. Among diagnostic tools, anatomic pathology is effective in recognizing or excluding infectious diseases based on morphological changes in organs in affected species [3] [4] [5] . Human and veterinary pathologists are familiar with their own fields. However, German physician Rudolph Virchow (1821-1902), a towering figure in 19 th medicine and pathology, stated, "Between animal and human medicine, there is no dividing line-nor should there be" while working on the zoonosis of trichinosis and hydatid disease [6, 7] . This emphasis based on diseases across species lines established the concept of "one medicine" and led to the development of comparative medicine and comparative pathology.

The diagnosis of infectious diseases, especially zoonosis, requires the collaborative efforts of physicians, epidemiologists, microbiologists, parasitologists, and pathologists, as well as veterinarians to seek causal agents. Anatomic pathologists are capable of analyzing and interpreting anatomical or functional manifestations of diseases from autopsy, biopsy and cytology materials using routine processes and advanced diagnostic skills. They can provide important clues to the diagnostic team in characterization of diseases [3, 8, 9] . Years of experience have shown that data obtained from animal necropsies can be useful in determining the cause of death, which allows comparison with human counterpart diseases. Histopathological and cytopathological observations often allow for establishment of a definite diagnosis or exclusion of a wide variety of diseases. Compared with other diagnostic methods such as culture, immunodiagnosis and molecular biology, anatomic pathology is safe, economical, fast and reliable. It can help provide a disease diagnosis using formalin-fixed tissues, and direct visualization of lesions with fewer falsenegative results.

Although disease-associated microbes are numerous, morphologic patterns of tissue reaction caused by microbes are limited. Therefore, the interactions between microbes and host determine the histologic changes in the target tissues. This allows anatomic pathologists to analyze rare or unknown pathogens and quickly report their findings to a diagnostic team, which gathers information from the pathological, microbiological, immunological and molecular aspects to confirm disease. In pathological study, a routine hematoxylin and eosin (H&E) stained section can directly visualize some infectious agents or their products (e.g. bacterial clumps, most protozoans, all helminthes and viral inclusion bodies) within lesions ( 

It is very difficult to predict when and where the next zoonosis will emerge and the ultimate outcome depends on myriad interconnected factors. Thus, rapid and efficient collaboration based on the one medicine concept is necessary. Comparative pathology particularly focuses on comparison of the disease Granulomatous inflammation Toxocara spp. migration Absence/minimal reaction Trichinellosis (Fig. 1) , Toxocara spp. migration Prions

Vacuolation of neurons and neuropil Scrapie (Fig. 2) , bovine spongiform encephalopathy, variant Creutzfeldt-Jakob disease (Fig. 3 

Technique Use Acid-fast stain Mycobacteria (Fig. 5) , Nocardia, cryptosporidium Brown-Brenn stain Gram +, Gram -Grocott's methenamine silver stain Fungi Immunohistochemistry

Antigen detection (Fig. 6 ) In situ hybridization Nucleic acid detection (Fig. 7 ) In situ polymerase chain reaction Nucleic acid detection Mucicarmine stain Cryptococci (Fig. 8 ) Periodic acid-Schiff stain Fungi (Fig. 9) , amebae Transmission electron microscopy Ultrastructure of target cells or microbes (Fig. 10 ) process in humans and other animals. To solve the complexities of emergence and re-emergence of zoonoses, effective and integrated collaboration between human and veterinary pathology is needed. With the use of morphologic features and auxiliary special techniques, anatomic pathologists contribute greatly to the diagnosis and consequent management of zoonoses (Table 4) . Retrospective case studies of recently occurring zoonoses reflect the importance of diagnostic pathology with its use of morphologic similarities in disease diagnosis. In 2003, an outbreak of severe acute respiratory syndrome (SARS) occurred in several countries and caused human deaths. The cause of the disease has been attributed to a coronavirus. Coronaviruses in animal species have been well known for years. In coronavirus mouse hepatitis virus (MHV), multinucleated syncytial giant cells (Fig. 11) in lesions of the liver and colon share common features with one of the characteristic lesions of SARS (Fig. 12) [16, 17] . Further study indicated that intranasal infection of A/J mice with MHV strain 1 produced pulmonary pathologic features of SARS, including interstitial pneumonitis, dense macrophage infiltrates, giant cells, and hyaline membranes, resulting in death in all animals [17, 18] .

Outbreaks of equine Hendra virus infection in Australia in 1994 and Nipah virus infection in Malaysia in 1998 both caused mortalities in humans, horses and pigs. The two viruses are now classified as a new genus Henipahvirus in the family Paramyxoviridae. In past years, paramyxoviruses have caused devastating mortality in humans and major economic loss from animal outbreaks, such as that seen in measles in humans, canine distemper in canine species, and rinderpest in cattle, as well as Newcastle disease in poultry. The most commonly affected organs are those in the respiratory, gastrointestinal and nervous systems. Among the lesions, syncytial cells throughout the epithelium and in the vascular endothelium are a characteristic diagnostic feature [19] .

Examples of scrapie in sheep versus kuru, and bovine spongiform encephalopathy in cattle versus variant Creutzfeldt-Jakob disease show common features of vacuolation of neuronal cell bodies and processes, spongiform changes in neuropil, no inflammatory infiltrates, and astrogliosis in the central nervous system [20] . Important morphologic observations from veterinary and human diagnostic pathologists provide valuable information in the exploration of mysterious diseases, such as prion diseases.

Streptococcus suis type 2 infection is a reemerging zoonosis and is transmitted from pigs to humans through close contact. An infection in Sichuan, China, in 2005 caused 215 cases of human disease and 39 deaths. Purulent meningitis was the most common finding in both human and pig cases [21, 22] . Routine H&E sections plus immunohistochemical staining provided rapid diagnosis and contributed greatly to the treatment of the disease. 

Humans and other animals live in an unprecedented era in which emerging and re-emerging zoonoses can occur anywhere and anytime and the consequences can be severe. To control and prevent zoonotic diseases, human medicine and veterinary medicine should not be separate and independent sciences. Through the one medicine discipline, anatomic pathologists contribute valuable information to the diagnostic team by interpreting and analyzing morphologic changes. In Taiwan, this interaction was established through the Chinese Society for Comparative Pathology in 1994.

In 2005, proceedings from the conferences of the society were published, and work continues in this area. We believe that comparative pathology will play an important role in the diagnosis, surveillance and control of unpredictable emerging and re-emerging zoonoses. 

Emerging zoonotic epidemics in the interconnected global community

A massive outbreak in Milwaukee of cryptosporidium infection transmitted through the public water supply

Infectious disease pathology

Pathology and emerging infections-quo vadimus?

The importance of the autopsy in emerging and reemerging infectious diseases

Avian influenza: Virchow's reminder

Interrelations of human and veterinary medicine; discussion of some aspects of comparative dermatology

Will pathologists play as important a role in the future as they have in the past against the challenge of infectious diseases

The emerging role of pathology in factious diseases

Intestinal cryptosporidiosis of pigs in Taiwan

Cryptosporidiosis in Tanzanian goat kids: scanning and transmission electron microscopic observations

Infectious diseases

Transmission and scanning electron microscopy of host cell entry by Toxoplasma gondii

Detection of Streptococcus suis by in situ hybridization, indirect immunofluorescence, and peroxidase-antiperoxidase assays in formalin-fixed, paraffin-embedded tissue sections from pigs

A non-biotin polymerized horseradish-peroxidase method for the immunohistochemical diagnosis of canine distemper

Immunohistochemical diagnosis of mouse hepatitis virus and Mycoplasma pulmonis infection with murine antiserum

Pulmonary pathological features in coronavirus associated with severe acute respiratory syndrome (SARS)

Murine hepatitis virus strain 1 produces a clinically relevant model of severe acute respiratory syndrome in A/J mice

Nervous system

Pathology and molecular diagnosis of transmissible spongiform encephalopathy

Streptococcal diseases

Streptococcal toxic shock syndrome caused by Streptococcus suis serotype 2

We are extremely grateful to Dr Chin-Cheng Lee of Shin Kong Wu-Ho-Su Memorial Hospital, Dr Cheng-Hsiang Hsiao of National Taiwan University Hospital, Dr Lin-Lin Chueh of National Taiwan University, and Dr Chung-Tiang Liang of the National Laboratory Animal Center for their kindness in providing the valuable photos in this article.