Enterocytozoon bieneusi as a cause of proliferative serositis in simian immunodeficiency virus-infected immunodeficient macaques part-2

Enterocytozoon bieneusi is the most common microsporidian parasite in human patients with acquired immunodeficiency syndrome (AIDS), and since its recognition in 1985, it has been associated with a severe enteropathy and biliary cirrhosis in these patients.1-3 Microsporidia are obligate intracellular parasites that lack mitochondria and use a unique polar tube apparatus to infect the host cell.4,5 Despite its common occurrence, basic aspects of parasite biology and host immunity are poorly understood. There is currently no effective treatment or rational approach to prevention. Until recently, advances have been hampered by the lack of suitable animal models and in vitro systems to cultivate the organism.6

We and others recently described E bieneusi as a spontaneous infection of both immunologically normal and simian immunodeficiency virus (SN)-infected macaques (Maraca mulatta, Maraca cyclopis, and Maraca nemestrina).7,8 The organism can be localized to the cytoplasm of epithelial cells of the gallbladder, bile ducts, and small intestine, where it is associated with a proliferative cholecystitis, cholangiohepatitis, and enteropathy, which closely resembles the conditions seen in human immunodeficiency virus (HIV)-infected human patients. Since its initial recognition, we have shown that this Enterocytozoon is nearly identical to the human-derived E bieneusi at the light, ultrastructural, and genetic level.7-9 Human and rhesus-derived E bieneusi sequences share 99.5% nucleic acid identity over a 2.0-kb fragment of the ribosomal gene complex.10 These observations suggest that rhesus macaques may serve as an animal model of human E bieneusi infection.

Herein we describe a unique proliferative serositis associated with E bieneusi infection of mesothelial cells in immunodeficient rhesus macaques. Identification of the organism within these lesions required the sensitive techniques of in situ hybridization (ISH) and polymerase chain reaction (PCR). This study shows that E bieneusi can disseminate in the immunocompromised host and should be considered in cases of proliferative serositis and pleuritis of unknown cause.

MATERIALS AND METHODS

Animal Housing and Inoculations

Macaques were housed at the New England Regional Primate Research Center in a centralized biolevel 3 containment facility in accordance with standards of the Association for Assessment and Accreditation of Laboratory Animal Care and Harvard Medical School's Animal Care and Use Committee.

Animals were inoculated intravenously with 1 of 2 pathogenic strains of SIV (SIVmac251 or SIVmac239), the history, preparation, and in vivo and in vitro properties of which have been described and reviewed extensively.11-13 Animals inoculated with these viruses were included in a variety of infectivity, pathogenesis, and vaccine studies and received no antiretroviral agents or antimicrobial prophylaxis. The monkeys were monitored closely and euthanized when moribund or deemed necessary by the veterinary staff. Complete postmortem examinations were performed on all animals, and representative samples of tissue were taken for formalin fixation, freezing, and electron microscopy.

Retrospective Analysis

The index case (Mm 320-94) was identified by evaluation of sections of duodenum and common bile duct examined by ISH for E bieneusi RNA. This monkey had severe cholangiohepatitis and choledochitis and a unique proliferative serositis of the intestines. Intracellular Enterocytozoon organisms were identified within this proliferative inflammatory tissue by ISH. Following the recognition of the index case, a retrospective analysis of computerized pathology records was conducted of all SIV infected, immunodeficient macaques who died between September 1991 and March 1999 (n = 225). This review revealed a series of animals with a diagnosis of peritonitis of unknown cause (n = 16). These cases were subjected to further analysis by ISH, immunohistochemistry (IHC), and PCR.

Enterocytozoon bieneusi as a cause of proliferative serositis in simian immunodeficiency virus-infected immunodeficient macaques part-1

Context.--Enterocytozoon bieneusi is the most frequent microsporidian parasite of human patients with acquired immunodeficiency syndrome and is a significant cause of diarrhea and wasting. Recently, this organism has also been recognized as a spontaneous infection of several species of captive macaques. As in humans, E bieneusi frequently causes enteropathy and cholangiohepatitis in immunodeficient simian immunodeficiency virus (SIV)-infected macaques.

Objective.--To examine E bieneusi as an etiologic agent of nonsuppurative proliferative serositis in immunodeficient rhesus macaques (Macaca mulatta).

Design.--Retrospective analysis of necropsy material obtained from immunodeficient SIV infected rhesus macaques.
Results.--Examination of SIV-infected rhesus macaques (n = 225) revealed E bieneusi proliferative serositis in 7 of

16 cases of peritonitis of unknown origin. The organism could be identified by in situ hybridization and polymerase chain reaction in sections of pleura and peritoneum obtained at necropsy. Serositis was always accompanied by moderate-to-severe infection of the alimentary tract, and morphologic evidence suggested dissemination through efferent lymphatics. Colabeling experiments revealed most infected cells to be cytokeratin positive and less frequently positive for the macrophage marker CD68. Sequencing of a 607-base pair segment of the small subunit ribosomal gene revealed 100% identity to sequences obtained from rhesus macaques (Genbank accession AF023245) and human patients (Genbank accession AF024657 and L16868).

Conclusions.--These findings indicate that E bieneusi disseminates in immunodeficient macaques and may be a cause of peritonitis in the immunocompromised host.

Systemic lupus erythematosus serositis

The imaging appearances of a case of systemic lupus erythematosus, which manifested initially as a serositis, is described. Barium small bowel study showed segments of spiculation with tethering, angulation, and obstruction. On computed tomography there was ascites and segments of asymmetrical thickening of small bowel wall were observed. Laparotomy revealed extensive patchy serosai and peritoneal plaques but biopsy of these lesions did not lead to a definitive diagnosis. The diagnosis was made on the basis of marked elevation of antinuclear and anti-double stranded DNA antibodies.

http://www3.interscience.wiley.com/

Proventricular Dilatation Disease (PDD)

In recent years, the incidence of Proventricular Dilatation Disease has been increasing at an alarming rate. Originally termed Macaw Wasting Disease, PDD has been identified in many species of psittacine birds, most commonly in African Greys, Cockatoos, Eclectus, and Macaws. PDD is three times more likely to affect adults than juveniles and is responsible for symptoms such as:

decreased or increased appetite; weight loss; lethargy; regurgitation; the passage of undigested seeds or voluminous stools if on a pelleted ration; lameness; weakness; ataxia (loss of balance); tremors; and other neurologic symptoms.

There is strong evidence that PDD is caused by a virus and; therefore, may be transmitted to other birds creating a hazardous situation in a group of birds. A diagnosis of PDD can only be definitively made by the identification of a lymphoplasmacytic ganglioneuritis in biopsy specimens of the crop (up to a 75% sensitivity), and/or the proventriculus (stomach) or ventriculus (gizzard). Symptoms of this disease occur specifically due to the ganglionueritis affecting the automatic motility of the digestive tract and other parts of the nervous system .

Infected birds may show no symptoms for more than 2 years, but can be a source of the virus for long periods of time. PDD is eventually fatal in all cases regardless of whether symptoms of regurgitation, malabsorption, or nervous system involvement occur. The virus is very unstable and quickly dies outside of the bird so infected birds should be isolated in an outdoor aviary. When PDD is identified within a group of birds, proper hygiene, isolation, and quarantine procedures must be adhered to since only time will tell if other birds are affected. Thanks to the work of veterinarians in research programs, better control measures including vaccination may become available.

It is important to note that there are many diseases which mimic PDD and each of these must be carefully considered when symptoms suggestive of PDD occur. These include:
# gastric nematode infections capable of causing weight loss, anemia, and signs of gastric impaction (anorexia, regurgitation, scant feces);
# protozoa infections including trichomoniasis and cryptosporidiosis;
# bacterial infections;
# fungal infections;
# candidiasis;
# mycobacterial infections;
# viral infections such as Avian Viral Serositis, Adenovirus, and Paramyxovirus III
# ingestion of foreign material (metal objects, feeding tubes, plastics, grit, feathers, substrate bedding) that can cause signs of gastric (proventriculus and/or ventriculus) obstruction, impaction, and may be complicated by perforation, abscessation, or peritonitis;
# heavy metal toxicity (esp. lead) which can be accompanied by sings of esophageal or proventricular dilatation, intestinal ileus (paralysis), impaction, abnormal droppings, and neurologic signs;
# hypervitaminosis D and the accompanying mineralization of digestive organs;
# impaction or signs of maldigestion due to disorders of the lining of the ventriculus (known as the koilin layer) that can be caused by zinc and copper toxicity, fungal infection, candidiasis, parasitic infection, internal papillomatosis, and vitamin D toxicosis;
# ulceration and perforation of the ventriculus (gizzard) due to koilin disorders;
# vitamin e/selenium deficiency;
# gastric tumors or other masses causing obstruction or the digestive tract;
# pancreatitis;
# and any systemic illness.

Dr Paul Skellenger

Lupus - 4 Different Categories

Lupus is a disease that forces the immune system to attack healthy tissue. It affects about 1.5 million Americans. Ninety percent of these Americans are women. Lupus is a very difficult disease to diagnose because each lupus patient can display different symptoms. The number of symptoms can also vary between patients. There are 4 different categories of lupus.

Systemic lupus erythematosus (SLE) constitute about 70 percent of the cases of lupus. About 15 percent of the people who have SLE exhibit symptoms during their teen years. This is the most dangerous form of lupus. In this form of lupus, the immune system attacks any system or organ in the body including the joints, skin, lungs, heart, blood, blood vessels, kidney, heart, liver, brain, tendons, pancreas, or nervous system. People between the ages of 15 and 44 are the most likely to develop SLE. The symptoms for SLE can range from being harmless to life threatening. Over 50 percent of all systemic lupus patients in the United States have some degree of brain inflammation. Between 3 and 20 percent suffer strokes. Some of the other more common symptoms are kidney damage, chronic fatigue and painful or swollen joints. Many people with SLE find that the ultraviolet rays from the sun or fluorescent lights make their condition worse. Other symptoms may include an unexplained fever, muscle aches, loss of appetite, hair loss, a butterfly-shaped rash across the nose and cheeks (malar), sores in the nose or mouth, serositis, seizures and a lower than normal number of red blood cells (anemia), white blood cells, or platelets. In addition, about 95% of people with SLE have a positive ANA test.

Discoid lupus erythematosus (DLE) is less harmful than SLE because it only affects the skin. DLE causes disc-shaped, red, raised rashes (discoid) to appear on the cheeks, face, neck, scalp, ears, or other parts of the body. These rashes are much more pronounced than those caused by SLE. They can become scaly and thick and last for years. They can also cause scarring. Only 10 to 15 percent of the lupus cases are DLE cases. Also about 10 percent of DLE patients will develop SLE.

Drug-induced lupus erythematosus (DILE) is caused by the use of certain drugs. Some of these drugs include hydralazine, procainamide, antiseizure medicines and acne medicines. Cocaine use and exposure to mercury can also induce DILE. Men are more likely to develop DILE because they need to use hydralazine and procainamide to treat certain heart conditions. Between 10,000 and 15,000 Americans are diagnosed with DILE every year. The symptoms of DILE are similar to those of SLE, although the symptoms are usually less pronounced. Some symptoms may appear only after taking a certain medication for months or years. Even if you stop taking the medication, the symptoms may not go away until several weeks or months have passed.

Neonatal lupus is a rare condition acquired by babies from mothers who have SLE or another immune system disorder. Scientists believe that the fetus acquires maternal antibodies, which can cause liver problems, skin rash and low blood cell counts. About 50 percent of these babies are born with a permanent heart defect. A pacemaker could be used to help with the heart defect.

About 10 percent of people with lupus also have symptoms characteristic of one or more additional connective tissue diseases such as rheumatoid arthritis, myositis, scleroderma and Sjogren's syndrome.

Michael Russell

Lupus Symptoms: Serositis

Serositis is the inflammation of the serous membranes (sacs) that surround organs. Serositis is one of the symptoms of lupus listed in the criteria of the American College of Rheumatology. This symptom is known to affect up to 45 percent of people with lupus. Examples of serositis that can be affected by lupus are pleurisy and pericarditis.

Pleurisy and the Lungs
Pleurisy is an inflammation of the membrane that surrounds both lungs. This membrane is called the pleura. Pleurisy can cause sharp chest pains that worsen when taking a deep breath or coughing.

Causes of Pleurisy
Pleurisy can be a result of many different medical conditions besides lupus. A doctor cannot diagnose lupus based on the presence of pleurisy alone. Some of the conditions that can lead to pleurisy are:

* lung infection
* pulmonary embolism (blood clot)
* lung cancer
* rheumatic fever
* connective tissue disorders
* radiation therapy
* pneumothorax (accumulation of gas in the pleural cavity)
*
pericarditis (inflammation of the pericardium, the sac that surrounds the heart).

Moving Towards the Lupus Diagnosis
Doctors will perform tests to determine the underlying cause of pleurisy. A chest x-ray can show conditions like pneumonia, tuberculosis, blood clots, cancer or fluid in the chest. Other tests can help determine whether pneumonia, rheumatic fever or blood clots exist. Doctors rule out all other conditions before making a diagnosis of lupus.

Pericarditis and the Heart
Another type of serositis related to lupus is pericarditis. Pericarditis is the inflammation of the sac (pericardium) that surrounds the heart. Pericarditis causes fluid to build up in the pericardium, making it more difficult for the heart to pump blood. The extra work of the heart causes chest pain. If the pericarditis is severe, the chest pain may increase with normal activity like swallowing, coughing or even breathing.

Causes of Pericarditis
Like pleurisy, pericarditis can be symptomatic of other illnesses besides lupus. Doctors must rule out other conditions before they consider pericarditis as a result of lupus. Other conditions that lead to pericarditis are:

* viral infection
* pus-producing infection
* tuberculosis
* kidney failure
* heart attack
* heart injury or trauma
* rheumatoid arthritis
* scleroderma
*
collagen vascular diseases.

Other Heart Involvement
Severe pericarditis can lead to inflammation of the heart muscle (myocarditis), although this condition is not a common symptom of lupus. Still, myocarditis can be dangerous because it can exist without the presence of symptoms. Consequently, myocarditis can be overlooked until the muscles of the heart become weak and lose effectiveness. This can lead to arrhythmias or irregular heart beats. Eventually, the heart's inability to meet circulatory demands can cause blood to back up in the heart and lead to heart failure.

Treatment of Serositis
Treating pericarditis or pleurisy is depends on the disease that is causing the condition. Therefore, diagnosing the original condition will dictate the best method of treatment. If a lupus diagnosis has been made, the treatment of these conditions follows treatment directions for other lupus symptoms. Patients are encouraged to get plenty of rest and to take non-steroidal anti-inflammatory medications (aspirin or ibuprofen). Persistent pain and inflammation may require a course of corticosteroids such as prednisone

www.about-autoimmune-diseases.com