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Three South African patients with severe Rickettsia conorii infection had complicated courses of illness with 2 fatal cases and 1 with gangrene of multiple digits. Immunofluorescent organisms of R. conorii were demonstrated in vascular endothelium of brain, leptomeninges, renal glomerular arterioles and capillaries, renal arteries and veins, myocardial capillaries and arteries, pulmonary alveolar capillaries, pancreatic septa, splenic arterioles, and dermis. Rickettsiae were also observed in hepatic sinusoidal lining cells, splenic and lymph node macrophages, and the blood vessels of the partially viable zone of the amputated digits. Pathologic lesions included cerebral and cerebellar perivascular mononuclear leukocytes, mild mononuclear leptomeningitis, glomerular arteriolitis, vascular and perivascular mononuclear cell-rich inflammatory foci in the kidney, pancreas, skin, and myocardium, hepatocellular necrosis, and pulmonary edema. The sites of lesions and rickettsiae showed strong topographical correlation. Thrombi and hemorrhage occurred in a minority of the sites of vascular injury. Rickettsiae were the apparent direct cause of meningoencephalitis, peripheral gangrene, and other foci of vascular injury. Fatal R. conorii infection with disseminated organ involvement emphasizes the pathogenic potential of this disease.

Canine ehrlichiosis was diagnosed in wolves, dogs, and wolf-dog crosses at a small zoo in northcentral Florida. Five of 9 adult canids and all 8 pups confined to a common kennel died as a result of the infection. The epizootic was associated with a massive Rhipicephalus sanguineus infestation. Hematologic and pathologic findings in an adult wolf-dog cross that died were characteristic of canine ehrlichiosis. That animal and four other canids were seropositive for Ehrlichia canis. No deaths occurred following the oral treatment of remaining canids with tetracycline hydrochloride and the treatment of canids and premises with acaricides.

Potomac horse fever was reproduced in 15 ponies by transfusion of whole blood originally from two natural cases and subsequently from ponies infected by the transfusions. Incubation periods varied from 9 to 15 days. Affected ponies developed varying degrees of fever, diarrhea, anorexia, depression, and leukopenia. Eleven affected ponies were killed, three died in the acute phase of the disease, and one did not show clinical signs. The most consistent post-mortem findings were fluid contents in the cecum and large colon, and areas of hyperemia (of inconstant degree and distribution) in mucosae of both small and large intestines. Multifocal areas of necrosis occurred in mucous membranes. Ehrlichial organisms were most common in the cytoplasm of epithelial cells, macrophages, and mast cells of the large colon.

We report 3 cases of rickettsial hepatitis observed in the Lyon area which were secondary to boutonneuse fever. The temperature was elevated and clinical signs were an often painful hepatomegaly and digestive disorders. These signs are only indicative when accompanied by atypical pneumonopathy or exantherma. Indeed, if the inflammatory syndrome is clear, hepatic function is little perturbed. Diagnosis is sometimes influenced by the epidemiological situation, and depends on serologic tests and histological evidence of granulomatous hepatitis (2 of the 3 cases here). The successful antibiotic treatment shows that patients presenting febrile granulomatous hepatitis should be tested for rickettsiosis.

Dogs with acute Ehrlichia canis infection showed the established clinical features of acute ehrlichiosis and had thrombocytopenia, anemia, increased serum glutamic pyruvic transaminase activity, and decreased total serum protein and albumin concentrations during the first weeks after infection, and increasing gamma globulin concentrations after the third week. Gross lesions in hemic and lymphoreticular tissues were transient lymphadenomegaly, splenomegaly, and increased red long-bone marrow. Lymphoreticular hyperplasia in the paracortical area of lymph nodes and in the splenic red pulp occurred during the second week of infection. Later, small lymphocytes were replaced by medium-sized lymphocytes and plasma cells. Activity of germinal centers increased initially, as shown by numerous mitotic figures and macrophages, but diminished later, and the follicles blended with interfollicular and paracortical tissue because of a decrease in small lymphocytes in the mantle layer. We saw splenic hemorrhages near the perifollicular sinus, and vasculitis, most often phlebitis, in the kidney between weeks 2 and 4. Multifocal reticuloendothelial hyperplasia occurred in the liver during the early stage and injured adjacent hepatocytes by compression. Lesions typical of ehrlichiosis in these dogs were interstitial pneumonia, subendothelial aggregates of mononuclear cells in pulmonary blood vessels, renal periglomerular and perivenular plasmacytosis, hemopoietic hyperplasia, and perivascular cuffs of lymphocytes and plasma cells in many organs.

The histopathology of the thymus and spleen and the response of spleen cells to mitogenic stimuli were evaluated in Sprague-Dawley CF-1 mice infected with Ehrlichia risticii. Intraperitoneal injection of 10(4) or 10(6) E. risticii-infected U-937 cells into mice resulted in 100% morbidity and partial mortality. Thymic atrophy became significant between 1 and 2 weeks postinfection and remained for the duration of the study. The atrophy appeared associated with antecedent destruction and rarefaction of lymphocytes, resulting in the loss of corticomedullary demarcation. Splenomegaly was prominent; significantly increased weights were detected 7 days postinfection. Histopathologic examination revealed rarefaction of lymphocytes around central arteries, the presence of necrotic debris in histiocytes, and replacement of erythropoiesis by granulopoiesis in the red pulp. Marked and acute reduction of in vitro proliferative responses of spleen cells to concanavalin A (ConA) and phytohemagglutinin were observed in mice infected with 10(4) or 10(6) E. risticii-infected U-937 cells. Interleukin-2 activity in the supernatant of ConA-stimulated spleen cells was also severely reduced. Both changes were time- and dose-dependent and were not associated with decreased spleen cell viability. Neither morbidity nor mortality occurred in mice infected with 10(2) E. risticii-infected U-937 cells. Although there was temporal reduction in phytohemagglutinin-driven lymphocyte proliferation, reduction in neither ConA-driven lymphocyte proliferation nor interleukin-2 activity was observed with this dosage. All E. risticii-inoculated mice seroconverted between days 18 and 25, as detected by the indirect fluorescent-antibody procedure. The findings indicate for the first time the hypoimmune responsiveness and histopathologic changes in lymphoid organs associated with E. risticii infection.

Potomac horse fever is characterized by fever, anorexia, leukopenia, profuse watery diarrhea, dehydration, and high mortality. An ultrastructural investigation was made to search for any unusual microorganisms in the digestive system, lymphatic organs, and blood cells of ponies that had developed clinical signs after transfusion with whole blood from horses naturally infected with Potomac horse fever. A consistent finding was the presence of rickettsial organisms in the wall of the intestinal tract of these ponies. The organisms were found mostly in the wall of the large colon, but fewer organisms were found in the small colon, jejunum, and cecum. The organisms were also detected in cultured blood monocytes. In the intestinal wall, many microorganisms were intracytoplasmic in deep glandular epithelial cells and mast cells. Microorganisms were also found in macrophages migrating between glandular epithelial cells in the lamina propria and submucosa. The microorganisms were round, very pleomorphic, and surrounded by a host membrane. They contained fine strands of DNA and ribosomes and were surrounded by double bileaflet membranes. Their ultrastructure was very similar to that of the genus Ehrlichia, a member of the family Rickettsiaceae. The high frequency of detection of the organism in the wall of the intestinal tract, especially in the large colon, indicates the presence of organotrophism in this organism. Infected blood monocytes may be the vehicle for transmission between organs and between animals. The characteristic severe diarrhea may be induced by the organism directly by impairing epithelial cell functions or indirectly by perturbing infected macrophages and mast cells in the intestinal wall or by both.

The recent increase in the incidence of boutonneuse fever in Italy provided the opportunity to study the pathology of six "taches noires," the lesions at the site of tick bite. The center of the lesion has either an ulcer or an area of necrosis of the epidermis and superficial dermis; in some cases the epidermis is intact. The alterations are mainly in the dermis and subcutaneous tissues where the small vessels show endothelial swelling and intramural and perivascular oedema and inflammation with macrophages, lymphocytes and smaller numbers of plasma cells, PMNs and eosinophils. In a few small arteries and fewer veins there are either nonocclusive mural or occlusive thrombi; there is no spatial or quantitative correlation between thrombosis and necrosis. We propose that cutaneous necrosis results from severe injury to many small vessels. Rickettsiae which had not been previously observed in "taches noires" were demonstrated in blood vessels by immunofluorescence, a finding that may be used as a means for early aetiological diagnosis of the disease. The "tache noire" is an excellent human model for localized rickettsial injury.

An epizootic of canine ehrlichiosis has occurred in military working dogs in Thailand. During the epizootic, 161 cases of ehrlichiosis were identified serologically in a population of 316 dogs, and 54 dogs exhibited clinical signs of disease. The epizootic is being controlled by elimination of ticks, by serologic identification and treatment of carriers with 30 mg/lb body weight/day of tetracycline for 14 days, and by continuous daily prophylactic administration of 3 mg/lb body weight/day of tetracycline. Clinical and serologic recognition of ehrlichiosis among pet dogs in widely separated regions of Thailand suggest that the disease has been endemic in Thailand for an extended time. Under such circumstances it is possible that pet and stray dogs have served as a source of infection for the epizootic in military working dogs.