Clinical and pathological findings of a newly recognized disease of elephants caused by endotheliotropic herpesviruses.

The unique clinical and pathological findings in nine Asian (Elephas maximus) and two African (Loxodonta africana) elephants from North American Zoos with a highly fatal disease caused by novel endotheliotropic herpesviruses are described. Identification of the viruses by molecular techniques and some epidemiological aspects of the disease were previously reported. Consensus primer polymerase chain reaction (PCR) combined with sequencing yielded molecular evidence that confirmed the presence of two novel but related herpesviruses associated with the disease, one in Asian elephants and the second in African elephants. Disease onset was acute, with lethargy, edema of the head and thoracic limbs, oral ulceration and cyanosis of the tongue followed by death of most animals in 1 to 7 days. Pertinent laboratory findings in two of three clinically evaluated animals included lymphocytopenia and thrombocytopenia. Two affected young Asian elephants recovered after a 3 to 4 wk course of therapy with the anti-herpesvirus drug famciclovir. Necropsy findings in the fatal cases included pericardial effusion and extensive petechial hemorrhages in the heart and throughout the peritoneal cavity, hepatomegaly, cyanosis of the tongue, intestinal hemorrhage, and ulceration. Histologically, there were extensive microhemorrhages and edema throughout the myocardium and mild, subacute myocarditis. Similar hemorrhagic lesions with inflammation were evident in the tongue, liver, and large intestine. Lesions in these target organs were accompanied by amphophilic to basophilic intranuclear viral inclusion bodies in capillary endothelial cells. Transmission electron microscopy of the endothelial inclusion bodies revealed 80 to 92 nm diameter viral capsids consistent with herpesvirus morphology. The short course of the herpesvirus infections, with sudden deaths in all but the two surviving elephants, was ascribed to acute cardiac failure attributed to herpesvirus-induced capillary injury with extensive myocardial hemorrhage and edema.

Bacterial flora, a possible source of serotonin in the intestine of adult female Ascaris suum.

The effect of intestinal bacteria on 5-hydroxytryptamine (5-HT, serotonin) level and 5-HT turnover rates in Ascaris suum intestine are presented. Ascaris suum were incubated in media containing antibiotics for 24 hr, and the bacterial flora in the anterior regions of the intestine of A. suum was eliminated. The bacteria were significantly reduced (> 99%) but not eliminated in the middle and posterior segments of the worm. The 5-HT level decreased in the intestine after 24 hr incubation in antibiotics, whereas the 5-HT turnover rate increased (131 ng/mg protein/hr). Two possible sources of 5-HT from the intestine were examined: the intestinal tissue itself and the microflora inhabiting the intestine. The 5-HT level in the microflora was 30% higher (72.6 ng/g) than the intestinal tissue (43.3 ng/g) in control samples (0 hr, no antibiotics). These values decreased significantly after 24 hr incubation in A. suum saline. The 5-HT values decreased to 18.6 ng/g in the presence and 28.6 ng/g in the absence of antibiotics. The 5-HT turnover rate during this time period indicated that as the number of bacteria declined, the 5-HT turnover rate also declined in the microflora, but the 5-HT turnover rate in the intestinal tissues increased. Results from these studies suggest that bacterial 5-HT may be contributing to the 5-HT level in A. suum intestinal tissue.

Identification of a novel 5-HTN (Nematoda) receptor from Ascaris suum muscle.

1. The abilities of various serotonergic drugs to bind with the 5-HT receptor of Ascaris suum muscle and to affect cyclic AMP levels in muscle tissue were examined. 2. Ligands which selectively interact with either the 5-HT1 or the 5-HT2 receptor in mammalian systems interact with the 5-HT receptor from A. suum muscle and increase cyclic AMP levels. 3. No binding of 5-HT3 ligands to 5-HT receptors from A. suum muscle was observed. 4. The 5-HT receptor of A. suum muscle should be called the 5-HTN (for Nematoda) receptor because its pharmacological and biochemical behaviors were different from those of mammalian 5-HT receptors.