Pathologic Anatomy of the Marburg Virus Disease

Abstract

In August and September, 1967, in Marburg, Frankfurt, and Belgrade, there appeared in institutes experimenting with animals serious human illnesses caused by contact with monkeys. Twenty-seven people were affected. Only in Marburg 23 persons were taken ill and, of these, 20 had had direct contact with blood, organs, or cell-derived cultures from monkeys imported from Uganda, of the type known as Cercopithecus aethiops. Three patients were infected through contact with people already sick. The period of incubation, which could be accurately deter-mined in patients who had had only a single contact with infectious material, was of five to seven days' duration. Twenty-five patients recovered slowly after being ill for approximately 15 days. Five patients died between the 8th and 16th day of illness. In the autopsies of the five patients who died in Marburg, we attempted to assemble the morphological findings. In order to deduce the development of the morphological alterations, we arranged the cases according to the duration of sickness, i.e., according to the elapsed time between the appearance of the first clinical symptoms and the moment of death. We then compared and correlated the results of these autopsies. In all of the deceased, it was possible to ascertain macroscopically a pronounced hyperemia of the leptomeninges and an edematous brain swelling, accompanying the usual signs of central death. In addition, signs of a hemorrhagic diathesis were present in the form of considerable bleedings into the skin and mucous membranes and occasionally also into the soft tissues and parenchymatous organs. With the exception of the last case, the stomach and large sections of the intestines were filled with blood and in part also with black stool, although it was impossible to discover any source of bleeding, such as ulcers or erosions. In none of the patients was the liver atrophic. It had in all cases a decidedly firm consistency and macroscopic analysis revealed no pathological findings worth mentioning. It should be stressed that in none of the cases there was an icteric or subicteric discoloration of the liver, ,of the skin or of other organs. The gallblader was noticeably enlarged and tightly filled. Hence the autopsies revealed, in agreement with the clinical findings, no indications of significant disturbances of the bilirubin excretion. The spleen was slightly enlarged in only two cases; the red pulpa was more frequently hardened, but revealed no irregularities macroscopically. In all cases, however, there was moderate swelling of the lymph nodes, which was especially evident on the hili and in the abdomen. The kidneys showed pale swelling in all cases. Finally, all of the deceased had a dark, blue-reddish, livid discoloration in the region of the external genitals near the scrotum or vulva. G. A. Martini et al. (eds.), Marburg Virus Disease © Springer-Verlag Berlin Heidelberg 1971 Pathologic Anatomy of the Marburg Virus Disease 51 The morphological picture of the lungs was not uniform. In general, the paren. chyma of the lungs appeared dry. In two cases, there was an unevenly developed bronchopneumonia. One case revealed scars and areas of fibrosis as well as bronchiectasis and an emphysema which had certainly originated long before this viral disease. The hearts of all the deceased were dilated. On surveying the macroscopical findings, it is evident that these morphological changes, taken separately or in combination, did not show a characteristic pattern which would allow classification in a well-known group of diseases. The histological examination of the organs provided considerably more in-formation. Surveying the histological findings, we are able to define six groups of alterations: 1. In almost all organs-with the exception of the skeletal muscles, the lungs and the skeleton-focal necroses appeared, which as a rule were not accompanied by an inflammatory reaction. These necroses were more conspicuous in the liver (see Marburg Virus Hepatitis) and in the lymphatic system. We were not, however, able to determine immediately where these necroses first appeared. Moreover, there were well-developed necroses in the testicles and ovaries, whereas they reached only minimal size in the kidneys, the adenohypophysis, the thyroid gland, the suprarenal gland and the skin. In all organs, the parenchymal cells were affected more by the necrobiosis than the mesenchymal structures. The findings in the patients who died in the later stages of the illness and the results of numerous liver biopsies on convalescent patients allowed us to conclude that the necrosis-at least in the liver-could be relatively quickly replaced through regeneration in spite of their great extent. 2. The lymphatic system reacted in a special way. In addition to the afore-mentioned necrosis of follicles, the red pulpa of the spleen and the medullary part of the lymph nodes revealed a loss of cells and an embedment of a finely granulated eosinophilic material the nature of which has not yet been indisputably deter-mined. We believe it possible that it contains some thrombocytic aggregates. There appeared later an increasing infiltration of plasmacellular elements and to some extent also of monocytes. The same cells were also discovered in large num-bers in the mucous membranes of the stomach and intestines. It seems probable that this plasmacellular and monocytoidal infiltration occurred in connection with an immunological process. 3. A constant finding in all autopsied cases was the appearance of peculiar basophilic bodies. They were predominantly round in form and had, as a rule, a diameter of 1-2, at most 3 -4 [1.. Repeatedly, one had the impression that the basophilia covered only a crescent-shaped area, surrounding an eosinophilic core. The basophilic bodies were found especially within the area or in the vicinity of necroses, in cell phagocytes but also extracellularly. Occasionally, they could also be found independently from necroses in the cytoplasma of otherwise apparently intact liver cells and kidney epithelia and also in the immediate vicinity of capillaries. Their coloration and histochemical properties indicated a high nucleic acid content, as it appears to the same degree in cell nuclei. These characteristics led at first to the conclusion that we were dealing with free or phagocytic fragments of necrotic cells; on second thought, 4·