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818 Part VI: The Erythrocyte Chapter 53: Hemolytic Anemia Resulting from Infections with Microorganisms 819

patients, examination of the blood film for malarial parasites should be and spleen. Normal red cells transfused into patients with bartonello-
4
made for at least 3 days after onset of symptoms because parasitemia sis meet a similar fate. A 130-kDa Bartonella protein that causes ery-
may not reach detectable levels for several days. throcytes to acquire trenches, indentations, and invaginations has been
90
purified from culture broths and has been called deformin. In addi-
TREATMENT tion, two B. bacilliformis genes, designated ialA and ialB, predicted to
Early treatment is important. The spread of antimalarial therapy has encode polypeptides of 170 amino acids (20.1 kDa) and of 186 amino
acids (19.9 kDa), respectively, greatly enhance the ability of Escherichia
resulted in major problems with drug resistance. Eradication of blood coli to invade erythrocytes. 91
forms can be achieved with individual agents or combinations of anti-
malarials. Artemisinins are the most effective agents for P. falciparum.
Numerous studies are in progress to determine the best single agent or CLINICAL FINDINGS
combination of agents to be used in the treatment of malaria in different As demonstrated by Carrión’s experiment, bartonellosis has two clinical
regions. Many such drugs are capable of producing severe hemolysis in stages. The acute hemolytic anemia, Oroya fever, represents the early,
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patients with G6PD deficiency, which is relevant in areas with endemic invasive stage of a chronic granulomatous disorder, the late stage of
malaria (Chap. 47). 87 which is designated verruca peruviana. Most patients manifest no clin-
ical symptoms during the Oroya fever phase, but when anemia does
PREVENTION occur, its onset is dramatic. Red counts as low as 750,000/μL (0.750
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An initial test of a P. falciparum sporozoite vaccine, administered intra- × 10 /L) have been documented. In addition to symptoms of anemia,
venously in five doses, has shown efficacy in a small number of exper- patients manifest thirst, anorexia, sweating, and generalized lymph-
imental subjects. The immunologic responses were closely correlated adenopathy. Spleen and liver enlargement are unusual. Large numbers
with vaccine dose. Although a very important step forward, the prac- of nucleated red cells appear in the blood film, and reticulocytosis is
tical limitations of five intravenous doses will have to be circumvented often striking. The white cell count is variable. Diagnosis is established
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for extensive application to susceptible populations. Another vaccine, by demonstrating the presence of the organism B. bacilliformis on the
RTS,S, is the first candidate to be tested in phase 3 clinical trials, but the erythrocytes. Giemsa-stained blood films reveal red-violet rods varying
preliminary results have been disappointing. Protection against clini- in length from 1 to 3 μm and in width from 0.25 to 0.2 μm. Although
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cal malaria in infants ranged between 30 and 50 percent and the effect molecular methods for diagnosis of Bartonella species are available, in
waned after several months. 88a a person with the clinical picture, the examination of the blood film can
be accomplished and therapy initiated, rapidly.
COURSE AND PROGNOSIS

When acute, unusually severe hemolysis occurs in the course of falci- TREATMENT AND COURSE
parum malaria (blackwater fever), the physician should be certain that Oroya fever responds well to treatment with penicillin, streptomy-
a hemolytic drug is not being administered to a G6PD-deficient indi- cin, chloramphenicol, and the tetracyclines. The mortality rate among
vidual. Transfusions may be needed with severe hemolysis, and if renal untreated patients is very high, but those who do survive undergo a sud-
failure occurs, extracorporeal dialysis may be required. With early insti- den transitional period in which the Bartonellae change from an elon-
tution of therapy the prognosis in malaria is excellent. However, when gated to a coccoid form, the number of parasitized cells decreases, and
treatment is delayed or the strain is resistant to the administered agent, the red cell count increases. Lymphocytosis and improved neutrophil
P. falciparum malaria may follow a rapid, fatal course. count are observed with disappearance of the fever and abatement
of other symptoms. The second stage of Bartonella infection, verruca
peruviana, is a nonhematologic disorder characterized by an eruption
BARTONELLOSIS (OROYA FEVER) over the face and extremities developing into bleeding warty tumors.
Other species of Bartonella cause human febrile infections such
EPIDEMIOLOGY as “cat-scratch fever,” or “trench fever,” or can infect individuals with
In 1885, Daniel A. Carrión, a medical student, inoculated himself with acquired immunodeficiency disease, but these disorders are not ordi-
blood obtained from a verrucous node of the skin of a patient with ver- narily associated with severe hemolytic anemia. 94–96
ruca peruviana. He developed a fatal hemolytic anemia with the charac-
teristics of Oroya fever, a disease that had first been observed some years BABESIOSIS
earlier among workers in a railroad construction project near the city
of Oroya in the Peruvian Andes. This fatal self-experiment established EPIDEMIOLOGY
the identity of the verrucosa form and the hemolytic phase of human
5,5a
bartonellosis, an infection that now bears the name Carrión disease. Babesiae are intraerythrocytic protozoas known as piroplasms. They are
Human bartonellosis is transmitted by the sandfly. transmitted by ticks that may infect many species of wild and domes-
tic animals. Humans occasionally become infected with Babesia microti
(North America) or Babesia divergens (Europe), species that normally
PATHOGENESIS parasitize rodents, and, deer, elk, and cattle, respectively. Other
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After a sandfly bite, the red blood cells become infected with Barto- Babesia-like piroplasms, such as Babesia WA1, first isolated from a patient
nella bacilliformis. It is believed that the organism does not grow within in the state of Washington, and Babesia MO1, isolated in Missouri, may
the red cell, but rather adheres to its exterior surface: When infected also produce human disease. Once thought to be rare, babesiosis is
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red cells are washed with citrated plasma, free organisms are found being recognized with increasing frequency. 99,100 The disease is usually
but the red cells are not hemolyzed. In hanging-drop cultures, masses tickborne in humans, but has also been transmitted by transfusion. 101–106
of organisms are clearly seen outside the erythrocytes, while the cells Cases of babesiosis, mostly caused by B. microti but also by Babesia WA1
themselves are intact. The osmotic fragility of the red cells is normal. species, have been transmitted by transfusion of blood from asymp-
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They are rapidly removed from the circulation, apparently both by liver tomatic infected blood donors. The risk of transfusion-transmitted

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