# 61 - 178 Donovanosis

### 178 Donovanosis

B. henselae) and avoidance and treatment of body louse infestation (for 
prevention of B. quintana). Primary prophylaxis is not recommended, 
but suppressive therapy with a macrolide or doxycycline is indicated in 
HIV-infected patients with bacillary angiomatosis or bacillary peliosis 
until CD4+ T-cell counts are >200/μL. Relapse may necessitate lifelong 
suppressive therapy in individual cases.

CARRIÓN’S DISEASE (OROYA FEVER AND 
VERRUGA PERUANA)
■
■DEFINITION AND ETIOLOGY
Carrión’s disease is a biphasic disease caused by B. bacilliformis. Oroya 
fever is the initial, bacteremic, systemic form, and verruga peruana—or 
“Peruvian warts”—is its late-onset, eruptive manifestation.
■
■EPIDEMIOLOGY AND PREVENTION
Infection is endemic to the geographically restricted Andes valleys of 
Peru, Ecuador, and Colombia (~500–3200 m above sea level). Sporadic 
epidemics occur. The disease is transmitted by the phlebotomine 
sandfly Lutzomyia verrucarum. Maternal-fetal transmission as well as 
transmission by blood transfusion have been reported. Humans are the 
only known reservoir of B. bacilliformis. Sandfly control measures (e.g., 
insecticides) and personal protection measures (e.g., repellents, screen­
ing, bed nets) may decrease the risk of infection.
■
■PATHOGENESIS
After inoculation by the sandfly, bacteria invade the blood ves­
sel endothelium and proliferate; the reticuloendothelial system and 
various organs also may be involved. Upon reentry into blood vessels, 

B. bacilliformis invades, replicates, and ultimately destroys erythro­
cytes, with consequent massive hemolysis and sudden, severe anemia. 
Microvascular thrombosis results in end-organ ischemia. Survivors 
sometimes develop cutaneous hemangiomatous lesions characterized 
by various inflammatory cells, endothelial proliferation, and the pres­
ence of B. bacilliformis (verruga peruana).
PART 5
Infectious Diseases
■
■CLINICAL MANIFESTATIONS
The incubation period is 3 weeks (range, 2–14 weeks). Oroya fever 
may present as a nonspecific bacteremic febrile illness without 
anemia or as an acute, severe hemolytic anemia with hepatomegaly 
and jaundice of rapid onset leading to vascular collapse and clouded 
sensorium. Myalgia, arthralgia, lymphadenopathy, and abdominal 
pain may develop. Temperature is elevated but not extremely so; high 
fever may suggest intercurrent infection. Subclinical asymptomatic 
infection also occurs. Secondary infection with Salmonella (typhi and 
non-typhi) is common, though other secondary infections have been 
reported and should be suspected when fever persists or recurs after 
defervescence. In verruga peruana, red, hemangioma-like, cutaneous 
vascular lesions of various sizes appear either weeks to months after 
systemic illness or with no previous suggestive history. These lesions 
persist for months up to 1 year. Mucosal and internal lesions also 
may develop.
■
■DIAGNOSIS AND APPROACH TO THE PATIENT
Systemic illness (with or without anemia) or the development of 
cutaneous lesions in a person who has been to an endemic area 
raises the possibility of B. bacilliformis infection. Severe anemia with 
exuberant reticulocytosis—and sometimes thrombocytopenia—can 
occur. In systemic illness, Giemsa-stained blood films may show 
typical intraerythrocytic bacilli. Blood and bone marrow cultures 
may be positive, but growth is slow (1−6 weeks) and requires lower 
incubation temperature. Serologic assays may be helpful. Diagnosis of 
verruga peruana is largely clinical, although biopsy may be required 
to confirm the diagnosis. Several PCR assays have been described; 
however, their role in diagnosis remains to be clinically validated. 
Differential diagnosis includes coendemic systemic febrile illnesses 
(e.g., typhoid fever, malaria, brucellosis) and diseases producing cuta­
neous vascular lesions (e.g., hemangiomata, bacillary angiomatosis, 
Kaposi’s sarcoma).

TREATMENT
Carrión’s Disease
(Table 177-2) Antibiotic therapy for systemic B. bacilliformis infec­
tion usually results in rapid defervescence. Additional antibiotic 
treatment of intercurrent infection is often required. Blood transfu­
sion may be necessary. Treatment of verruga peruana is not always 
required. Patients with numerous lesions, especially lesions that 
have been present for only a short period, may respond well to 
antibiotic therapy.
■
■COMPLICATIONS AND PROGNOSIS
Mortality rates associated with Oroya fever have been reported to be as 
high as 40% without treatment but are considerably lower (~10%) with 
treatment. Complications such as bacterial superinfection and neuro­
logic and cardiac manifestations occur frequently. Generalized massive 
edema (anasarca) and petechiae are associated with poor outcome. 
Permanent immunity usually develops.
■
■FURTHER READING
Fournier PE et al: Epidemiologic and clinical characteristics of 
Bartonella quintana and Bartonella henselae endocarditis: A study of 
48 patients. Medicine (Baltimore) 80:245, 2001.
Gomes C, Ruiz J: Carrion’s disease: The sound of silence. Clin Microbiol 
Rev 31:e56, 2018.
Koehler JE et al: Molecular epidemiology of Bartonella infections in 
patients with bacillary angiomatosis-peliosis. N Engl J Med 337:1876, 1997.
Landes M et al: Cat scratch disease presenting as fever of unknown 
origin is a unique clinical syndrome. Clin Infect Dis 71:2818, 2020.
Rolain JM et al: Recommendations for treatment of human infections 
caused by Bartonella species. Antimicrob Agents Chemother 48:1921, 
2004.
Rose SR, Koehler JE: Bartonella including cat scratch disease, in 
Principles and Practice of Infectious Diseases, 9th ed, GL Mandell et al 
(eds). Philadelphia, Elsevier, Inc. 2020, pp 2824–2843.
Wagner A, Dehio C: Role of distinct type-IV-secretion systems and 
secreted effector sets in host adaptation by pathogenic Bartonella spe­
cies. Cell Microbiol 21:e13004, 2019.
Nigel O’Farrell

Donovanosis
Donovanosis is a chronic, progressive bacterial infection that usually 
involves the genital region. The condition is generally regarded as a 
sexually transmitted infection of low infectivity. This infection has been 
known by many other names, the most common being granuloma 
inguinale.
■
■ETIOLOGY
The causative organism has been reclassified as Klebsiella granulomatis 
comb nov on the basis of phylogenetic analysis, although there is ongo­
ing debate about this decision. Some authorities consider the original 
nomenclature (Calymmatobacterium granulomatis) to be more appro­
priate in light of analysis of 16S rRNA gene sequences.
Donovanosis was first described in Calcutta in 1882, and the 
causative organism was recognized by Charles Donovan in Madras 
in 1905. He identified the characteristic Donovan bodies, measuring 

1.5 × 0.7 μm, in macrophages and the stratum malpighii. The organism 
was not reproducibly cultured until the mid-1990s, when its isolation 
in peripheral-blood monocytes and human epithelial cell lines was 
reported.

■
■EPIDEMIOLOGY
Donovanosis has an unusual geographic distribution that has included 
Papua New Guinea, parts of southern Africa, India, the Caribbean, 
French Guyana, Brazil, and Aboriginal communities in Australia. In 
Australia, donovanosis has been almost entirely eliminated through 
a sustained program backed by strong political commitment and 
resources at the primary health care level. In South Africa, donova­
nosis is also very close to elimination. Although few cases are now 
reported in the United States, donovanosis was once prevalent in this 
country, with 5000–10,000 cases recorded in 1947. The largest epi­
demic recorded was in Dutch South Guinea, where 10,000 cases were 
identified in a population of 15,000 (the Marind-anim) between 1922 
and 1952.
Donovanosis is associated with poor hygiene and is more common 
in lower socioeconomic groups than in those who are better off and in 
men than in women. Infection in sexual partners of index cases occurs 
to a limited extent. Donovanosis is a risk factor for HIV infection 
(Chap. 208).
Globally, the incidence of donovanosis has decreased significantly in 
recent times. This decline probably reflects a greater focus on effective 
management of genital ulcers because of their role in facilitating HIV 
transmission.
■
■CLINICAL FEATURES
A lesion starts as a papule or subcutaneous nodule that later ulcerates 
after trauma. The incubation period is uncertain, but experimental 
infections in humans indicate a duration of ~50 days. Four types 
of lesions have been described: (1) the classic ulcerogranulomatous 
lesion (Fig. 178-1), a beefy red ulcer that bleeds readily when touched; 
(2) a hypertrophic or verrucous ulcer with a raised irregular edge; (3) a 
necrotic, offensive-smelling ulcer causing tissue destruction; and (4) a 
sclerotic or cicatricial lesion with fibrous and scar tissue.
The genitals are affected in 90% of patients and the inguinal region 
in 10%. The most common sites of infection are the prepuce, coronal 
sulcus, frenum, and glans in men and the labia minora and fourchette 
in women. Cervical lesions may mimic cervical carcinoma. In men, 
lesions are associated with lack of circumcision. Lymphadenitis is 
uncommon. Extragenital lesions occur in 6% of cases and may involve 
the lip, gums, cheek, palate, pharynx, larynx, and chest. Hematogenous 
spread with involvement of liver and bone has been reported. During 
pregnancy, lesions tend to develop more quickly and respond more 
slowly to treatment. Polyarthritis and osteomyelitis are rare complica­
tions. In newborn infants, donovanosis may present with ear infection. 
Cases in children have been attributed to sitting on the laps of infected 
adults. As the incidence of donovanosis has decreased, the number of 
unusual case reports has appeared to be increasing.
Complications include neoplastic changes, pseudoelephantiasis, and 
stenosis of the urethra, vagina, or anus.
FIGURE 178-1  Ulcerogranulomatous penile lesion of donovanosis, with some 
hypertrophic features.

FIGURE 178-2  Pund cell stained by rapid Giemsa (RapiDiff) technique. Numerous 
Donovan bodies are visible.
CHAPTER 178
■
■DIAGNOSIS
A clinical diagnosis of donovanosis made by an experienced practitio­
ner on the basis of the lesion’s appearance usually has a high positive 
predictive value. The diagnosis is confirmed by microscopic identifi­
cation of Donovan bodies (Fig. 178-2) in tissue smears. Preparation 
of a good-quality smear is important. If donovanosis is suspected on 
clinical grounds, the smear for Donovan bodies should be taken before 
swab samples are collected to be tested for other causes of genital ulcer­
ation so that enough material can be collected from the ulcer. A swab 
should be rolled firmly over an ulcer previously cleaned with a dry 
swab to remove debris. Smears can be examined in a clinical setting by 
direct microscopy with a rapid Giemsa or Wright’s stain. Alternatively, 
a piece of granulation tissue crushed and spread between two slides can 
be used. Donovan bodies can be seen in large, mononuclear (Pund) 
cells as gram-negative intracytoplasmic cysts filled with deeply staining 
bodies that may have a safety-pin appearance. These cysts eventually 
rupture and release the infective organisms. Histologic changes include 
chronic inflammation with infiltration of plasma cells and neutrophils. 
Epithelial changes include ulceration, microabscesses, and elongation 
of rete ridges.
Donovanosis
A diagnostic polymerase chain reaction (PCR) test was based on the 
observation that two unique base changes in the phoE gene eliminate 
Hae111 restriction sites, enabling differentiation of K. granulomatis 
comb nov from related Klebsiella species. PCR analysis with a colori­
metric detection system can now be used in routine diagnostic labo­
ratories. A genital ulcer multiplex PCR that includes K. granulomatis 
has been developed. Serologic tests are only poorly specific and are not 
currently used.
The differential diagnosis of donovanosis includes primary syphilitic 
chancres, secondary syphilis (condylomata lata), chancroid, lympho­
granuloma venereum, genital herpes, neoplasm, and amebiasis. Mixed 
infections are common. Histologic appearances should be distinguished 
from those of rhinoscleroma, leishmaniasis, and histoplasmosis.
TREATMENT
Donovanosis
Many patients with donovanosis present quite late with extensive 
ulceration. They may be embarrassed and have low self-esteem 
related to their disease. Reassurance that they have a treatable