Bartonellosis Beyond the Andes
Abstract & Commentary
Synopsis: Bartonellosis is an infectious disease that has been well recognized since the time of the Incas. Documented bartonellosis outbreaks have been rare since the beginning of the 20th century; however, endemic regions include remote Andean villages in Peru, Ecuador, and Colombia situated at elevations of 500-3000 meters. Recent foci of bartonellosis have been reported from lower elevations of Ecuador, Colombia, and in the Pomabamba Province, Peru, in 1987.
Source: Ellis BA, et al. An outbreak of acute bartonellosis (Oroya fever) in the Urubamba region of Peru, 1998. Am J Trop Med Hyg 1999;61:344-349.
This interesting article is a case-control study conducted in collaboration with the Peruvian National Institutes of Health as an emergency response outbreak investigation. In all, 357 participants from 60 households were interviewed during an outbreak of bartonellosis, which occurred in a region not previously considered endemic for this disease. Both human blood and local insect specimens were evaluated and environmental assessments were performed. Most documented cases occurred in children who had fever, anemia, and characteristic coccobacilli observed in thin smears. Case patients reported sandfly bites more recently than control individuals of neighboring households, greater than 5 km away. Bartonella bacilliformis isolates from blood were confirmed by nucleotide sequencing. Specificity of blood smears was 96% using identification of bacterial isolates as the microbiological standard. Given that Peru is host to more than 700,000 tourists yearly, most of whom visit the Cuzco area, both visitors and travel medicine consultants must be aware of the risk of bartonellosis, as well as the disease manifestations. Preventive measures should include protection against sandfly exposures in endemic areas.
Comment by maria d. mileno, md
B. bacilliformis is the etiologic agent of the ancient sandfly-transmitted febrile hemolytic anemia (Oroyo fever) and chronic cutaneous angiomatosis (verruga peruana) found in Andean tropical Peru, Ecuador, and Colombia. The organism is a facultative 1 to 3 micron intracellular pleomorphic bacillus, with a poorly staining gram negative cell wall and 2-16 unipolar flagellae conferring a high degree of bacterial motility. Representations of bartonellosis can be seen in pottery and stone from the pre-Colombian era, as well as in lesions observed in a mummy. Chronicles of the Spanish conquistadors in Ecuador (soldiers sent to quell the rebellion of Diego de Almagro) detailed their illnesses, which were characterized by systemic symptoms and numerous cutaneous lesions that persisted for months.
Humans are the important reservoir hosts for B. bacilliformis. Bacteremia may persist for months after clinical recovery. A wildlife reservoir is thought to exist; however, no isolations of B. bacilliformis have ever been obtained from fauna of endemic areas. More than 500 different species of sandflies have been described, and Lutzomyia verrucarum is considered to be the actual vector in Peru. In endemic areas more than 6% of the population may have been infected, and 10% of these individuals are bacteremic at any given point. The majority of infections occur in children. Mothers in endemic areas are quite familiar with the skin lesions and know the risks of fever, severe complications, and death that may follow. Epidemics occur when immunologically naive persons are exposed to infection because of population migrations or the introduction of infected sandflies.
In terms of clinical manifestations of the disease, the incubation period for South American bartonellosis is approximately 21 days. The two clinical forms of the disease, Oroya fever and verruga peruana, may occur sequentially or at times with an intervening period that is clinically silent. Alternatively, either form may occur alone. In Oroya fever, the organism is introduced into the skin by the bite of a sandfly and is taken up by endothelial cells of capillaries, sinusoidal lining cells, and red blood cells. Bartonella species use a protein, deformin, to induce invaginations in the erythrocyte cell membrane and enter the red blood cell. Flagellar motility aids entry of the organism into cells. Systemic symptoms such as malaise, somnolence, anorexia, myalgias, headache, arthralgias, chills, dyspnea, and fever accompany erythrocyte parasitization, which may approach 100%. The mononuclear phagocytic system removes and destroys a large portion of infected red blood cells, resulting in severe anemia, hepatosplenomegaly, generalized lymphadenopathy, and jaundice. B. bacilliformis can invade endothelial cells in skin and lymph nodes. Severely infected patients may experience pericardial effusions, myocarditis, coma, convulsions, delirium, acute respiratory distress, and anasarca. The duration of bartonellosis during pregnancy is between one and six weeks, with a spectrum of illness that may range from mild to fatal. During pregnancy there may be transplacental infection, spontaneous abortions, and maternal deaths.
In the preantibiotic era there was a 40% mortality rate associated with acute bartonellosis. That figure is currently 8% in hospital settings and 88% for outbreaks that occur in remote rural areas. Death often occurs due to the frequent appearances of subsequent opportunistic infections. Salmonellosis has been the most frequently recognized fatal complication observed in hospitalized patients. Other infections, such as amebiasis, malaria, tuberculosis, and systemic infections by various enteric pathogens, complicate up to 45% of cases and contribute significantly to mortality. Without any preceding illness, or between two and 20 weeks after recovering from either a febrile illness or a syndrome of arthralgias and fever, a crop of skin lesions (verrucae) appears. These are painless erythematous 0.2 to 4 cm papules, nodules, or large angiomata appearing on the head and extremities. Occasionally they occur on the nasal, conjunctival, or oral mucosa, but have never been described within internal organs. A component of B. bacilliformis stimulates proliferation of human endothelial cells in vitro, and the formation of new blood vessels in vivo. Individual verrucae dry up and slough in a few weeks, leaving no scars. Crops of verrucae can occur for months or, exceptionally, for years.
For treatment, chloramphenicol is preferred for Oroya fever because of its activity against salmonellosis, which is a frequent, life-threatening secondary infection. Penicillin, fluoroquinolones (ciprofloxacin and norfloxacin only), erythromycin, and tetracyclines have also been used. Severe anemia, requiring transfusions, occurs in approximately 10% of patients; however, once the infection is controlled, the recovery from anemia is surprisingly rapid. Short courses of dexamethasone have been used for severe cerebral complications (coma, convulsions, and cerebral edema). Oral rifampicin (10 mg/kg/day for 14-21 days) is the most effective treatment for verrucae. Interestingly, patients in the current Peruvian outbreak did not manifest verrucae.
Prevention and pretravel advice should include information regarding repellents, insecticides—similar to prevention measures for malaria. However, fine-mesh netting is required and it must be small enough to exclude sandflies (3 mm), which are smaller than mosquitoes. Biting tends to occur at dusk. While travelers may not care to learn the gory details concerning bartonellosis, emphasis can be placed upon personal protection measures in order to avoid this disease, in addition to malaria.
Reference
1. Walker DH, et al. Bartonelloses. In: Guerrant RL, Walker DH, Weller PF, eds. Tropical Infectious Diseases. Principles, Pathogens and Practice. Philadelphia, PA: Churchill Livingstone; 1999:492-497.
Verrucae peruana are:
a. common skin manifestations of B. bacilliformis infections.
b. disfiguring oral lesions that do not heal.
c. only seen during bacteremia with B. bacilliformis.
d. responsive to be the same agents used to treat bloodstream infection with B. bacilliformis.
e. None of the above
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