CHAPTER XXXV

VERRUGA PERUVIANA AND OROYA FEVER

It is thought that Oroya fever was the disease which proved so fatal to Pizarro’s army in the 16th century. In 1870, great interest was aroused in these diseases on account of their prevalence in the workmen constructing the railroad from Lima to Oroya, a town in the Andes. At this time there was much conflict of opinion as to whether the two diseases were identical. In 1885, Carrion, a medical student of Lima, inoculated himself with the blood from a verruga lesion and died from Oroya fever about one month later. As the result of this it seemed to be established that infection with verruga material would produce the serious first-stage fever and many call the fever Carrion’s disease. Consequently these two diseases have, until recently, been considered as two stages of the same disease, the usual idea being that Oroya fever is the first stage, following which, provided the patient does not die from this very fatal fever, there sets in an eruption which is the second or verruga stage. In order to reconcile the observations of the development of the eruptive stage without a severe, febrile, preliminary one of three or four weeks, it was considered that the first stage might be exceedingly mild.

Strong and his colleagues, however, inoculated a volunteer with material from verruga lesions and sixteen days later the eruption appeared without the preliminary fever and anaemia that are so characteristic of Oroya fever, and it is now recognized that they are two distinct entities.

OROYA FEVER

GENERAL CONSIDERATIONS

Oroya fever is an acute, infectious disease, often terminating fatally, caused by the _Bartonella bacilliformis_, and characterized by an insidious onset, irregular fever, pains in the bones and a rapidly developing anaemia of the pernicious anaemia type.

The disease is chiefly found in towns situated in narrow, wind-protected valleys of the west side of the Andes, at elevations of from 3000 to 9000 feet. Townsend has suggested that a species of _Phlebotomus_, _P. verrucarum_, which is very prevalent, may be the transmitting agent. This investigator believes that verruga and Oroya fever are the same disease. It may be stated that malaria and enteric fevers, as well as verruga, are common in the localities where Oroya fever prevails and much of the confusion in the literature of Oroya fever is due to failure to differentiate the better known conditions. Strong noted that Oroya fever was common from January to April,

## particularly towards the close of the warm, rainy season. Cases were

rare in April and May and did not occur in the months of June, July and August. He notes that verruga was not uncommon at the time when Oroya fever was not occurring. Concomitant infection with Oroya fever and verruga may occur but this is also true of malaria or malaria and verruga may exist at the same time.

Barton isolated a paratyphoid bacillus from the blood of a patient, besides which other bacteria have also been isolated. In 1909, Barton noted certain rod-like organisms in the red cells of Oroya fever patients which he considered protozoal in nature.

Strong and his colleagues found in the blood of Oroya fever cases rod-shaped forms in the red cells, varying from 1 to 2 microns in length, the red cells containing from 1 to 30 of these elements.

A study of sections of lymphatic glands of severe fatal cases showed great numbers of these bodies packed in the endothelial cells. These cells rupture and set free the organisms.

Intravenous inoculation of blood containing these elements into monkeys and rabbits was negative in result. Strong failed to cultivate the organism. These organisms were considered as intermediate between bacteria and protozoa. They are closely related to _Grahamella_ and the Harvard commission has proposed the name _Bartonella bacilliformis_. In many ways they resemble piroplasms, especially _Theileria_.

PATHOLOGY

At autopsy the skin shows the pale yellowish waxy hue of pernicious anaemia. The lymphatic glands are somewhat enlarged and may be oedematous. The heart is flabby and ecchymoses may be present in the pericardium. The spleen is enlarged, shows numerous infarctions and contains large amounts of pigment in the form of yellowish masses or granules deposited between the splenic cells and in the endothelial leucocytes. This pigment is like melanin in not giving the iron reaction. The liver likewise is enlarged, shows areas of toxic degeneration and contains moderate amounts of pigment. The femoral marrow is soft and dark red. Microscopically, the endothelial cells of the lymphatics distended with the causative organisms were

## particularly noted by Strong.

SYMPTOMATOLOGY

The incubation period is about three weeks and the onset of the disease is marked by malaise and apathy, to be followed by a rapidly developing anaemia, of the pernicious anaemia type, with an irregular fever of a remittent character fluctuating between 100° and 102°F. and only exceptionally going up to 104°F., and pains in head, joints and bones. The tenderness over the bones is undoubtedly associated with the marked changes going on in the bone marrow and is

## particularly marked over the sternum.

The patient rapidly develops a very severe anaemia and death results in 20 to 40% of cases in two or three weeks. Delirium is often noted.

The spleen and the lymphatic glands are somewhat enlarged. Associated with the profound anaemia there may be oedema of legs and about joints and functional cardiac murmurs. The kidneys do not seem to be affected. There may be a diarrhoea in the later stages of the disease. There is no eruption in uncomplicated cases.

The most important findings in the disease are those in connection with the blood examination. The rod-shaped organisms, which are thought to be the cause of the disease, are somewhat difficult to observe in fresh blood preparations. They show definite motility within the red cells, particularly after warming the blood slide. The motion is a rather gliding one. In Romanowsky-stained preparations the 1 to 2 micron-long rods within the red cells may occur singly or in numbers of 4 or 5. V-shapes are frequently seen. The rod shows a bluish staining with a deep purplish-red chromatin-stained granule at one extremity. Rounded, oval or pear-shaped forms may also be seen.

While the parasites are present in great numbers in severe cases they may be very scarce in mild forms of the disease.

Very striking is the rapidly developing anaemia which frequently shows a red cell count of less than a million within a few days. Normoblasts are quite numerous and fulminating cases show numerous megaloblasts.

Polychromatophilia and poikilocytosis are noted.

In the red cells we have the picture of a rapidly developing pernicious anaemia The color index is above 1.

The leucocytes number about 20,000 of which 60 to 70% are neutrophiles. Immature neutrophiles, as the metamyelocyte, are very common.

PROPHYLAXIS AND TREATMENT

The transmitting agent not being known we are in the dark as to prevention. Evidence points to some arthropod biting at night as the incidence of the disease decreased when those working in the Oroya fever zone were compelled to leave the valleys before sundown. The treatment is largely one of nursing although some have reported favorably from the intravenous administration of salvarsan.

VERRUGA PERUVIANA

GENERAL CONSIDERATIONS

Verruga peruviana is an infectious eruptive disease, caused by an unidentified virus, lasting two or three months, and characterized by successive eruptions exhibiting two types of lesion,—the miliary and the nodular,—both of which show a pronounced tendency to ulceration and haemorrhage. The eruption of verruga somewhat resembles that of yaws and it was at one time suggested that verruga was simply yaws as influenced by high altitude. Strong and his colleagues found that they could infect rabbits intratesticularly and that lesions resembling those of man could be produced in dogs and monkeys by cutaneous and subcutaneous inoculations. The virus has been transmitted from monkey to monkey. The monkey is not as susceptible to the virus as man and the rabbit and dog less so. Inoculation of the monkey is not followed by a generalized eruption. The Wassermann reaction was negative. In extracts from the granulomatous lesions they found a very active haemolysin. It will be remembered that animals are not susceptible to Oroya fever blood inoculations.

From the fact that it is possible to inoculate a person by rubbing verruga material on a scarified surface it would seem that the infection might be transmitted by insects.

As regards the pathology of verruga, Cole has noted involvement of the lymphatic channels, which become obstructed by a cellular exudate, around which lymphatics are found plasma cells and fibroblasts. There is marked dilatation of the capillary blood vessels. The structure of these granulomatous tumors is very vascular, almost cavernous, hence the tendency to haemorrhage. The haemolysin may also be operative in the liability to haemorrhage.

Strong and his colleagues found the early lesions to consist of newly formed blood vessels lying in an oedematous connective tissue. The endothelial cells lining them may be in more than one layer. Around these blood vessels we have aggregations of cells which are considered as angioblasts. These angioblasts show frequent mitotic figures. There is a resemblance to a fibrosarcoma.

SYMPTOMATOLOGY AND TREATMENT

The period of incubation is about two weeks as shown by experimental inoculation but may be as long from the standpoint of clinical observation as forty days. At the onset we have rather severe pains of joints, especially the knees, ankles and wrists, together with a fever sometimes reaching 104°F. but usually not above 100°F. Following the eruption, the temperature usually subsides to normal in a few days. The eruption shows two types, the one with numerous, small, wart-like lesions, not exceeding the size of a small pea (2 to 5 mm.)—the miliary type, and the other, with less numerous but much larger nodular masses—the nodular type. The latter type is more rarely seen than the former.

[Illustration: FIG. 136.—Verruga Peruviana. (From Ruge and zur Verth.)]

_The Miliary Type._—The eruption is most abundant on the face and extensor surfaces of the extremities and less common on the trunk. In this type a pink macule appears which rapidly takes on a bright red color and becomes nodular. These nodules may be flat or somewhat pedunculated and bleed easily. At first smooth and shiny, it later on shrivels up without leaving a scar. This form of the eruption may involve the mucous membranes, as of conjunctivae, nose, pharynx, etc. In children the disease is usually of a mild type.

_The Nodular Type._—The _nodular eruption_ develops slowly and the lesions may become as large as a pigeon’s egg. They tend to become strangulated and then show as ulcerating, fungating masses which are a source of danger from haemorrhage. The nodular eruption does not invade mucous membranes and is usually confined to the regions of joints, as flexures of elbows, knees, etc.

The eruptions tend to come out in crops and the duration of the disease extends over two or three months.

_Treatment._—The ordinary principles of cleanliness apply to the care of the lesions to prevent secondary infections. When the large tumor-like masses begin to ulcerate or become gangrenous they should be excised. It must be remembered that dangerous bleeding may occur at unexpected times, for which reason the patients should be provided with styptics or compresses to prevent serious loss of blood.

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