What are the other Names for this Condition? (Also known as/Synonyms)

• Bartonella Bacilliformis Infection
• Oroya Fever
• Peruvian Wart

What is Carrion’s Disease? (Definition/Background Information)

• Carrion’s Disease is a bacterial illness endemic to the Andes Mountains in Western South America including Peru, Colombia, and Ecuador. It is caused by the bacterium Bartonella bacilliformis, which is transmitted through the bites of sandflies belonging to the genus Lutzomyia
• Carrion’s Disease is a biphasic illness with two distinct phases:
  • The acute phase is classically known as “Oroya Fever”. It occurs mostly in immunologically naive individuals; meaning that they have been exposed to the infection for the first time and their immune system is new to the infection. It is characterized by fever and hemolytic anemia. If not timely treated with antibiotics, Oroya Fever can lead to severe life-threatening complications
  • The chronic phase is the eruptive phase, classically known as “Verruga Peruana”. It is characterized by nodular skin lesions which are highly vascular and may bleed on touch. It is a benign condition which resolves in 3-6 months even without treatment. Verruga Peruana occurs in previously infected individuals, who may or may not have had an antecedent acute febrile illness
• The bacterium circulates in the blood of all patients during the acute phase. Therefore, the acute phase is most commonly diagnosed by direct observation of the bacteria in peripheral blood smears or culturing it from blood. The eruptive phase is diagnosed by histopathological examination of biopsy samples from the skin lesions
• There are highly effective antibiotics available for the treatment of Carrion’s Disease. However, the treatment requires prolonged courses of antibiotics, which can lead to the emergence of antibiotic resistance and several other side effects. Therefore, antibiotics should not be taken without the advice of a healthcare professional, and it is important to consult an infectious disease expert regarding antibiotic options
• Currently, there is no vaccine available for preventing Carrion’s Disease. Untreated individuals with the acute phase of disease have high mortality rates. A very small percentage of individuals develop the chronic phase; the lesions of which typically heal over several months with adequate treatment

Who gets Carrion’s Disease? (Age and Sex Distribution)

• Carrion’s Disease is a bacterial (infectious) disease endemic to the Andes Mountains in Western South America including Peru, Colombia, and Ecuador, with Peru being the most affected country
• Recently, it has been noted to emerge in new areas in Ecuador and Peru which seemingly did not have the infection earlier. This may likely be due to the expansion in sandfly (vector) distribution caused by global climate changes
• Due to a lack of population studies, the exact burden of the infection is not known. Few studies indicate that around half of the population below 25 years of age in the endemic areas may have contracted the infection, with majority being asymptomatic. It is more common in children due to lack of previous immunity
• Carrion’s Disease affects males slightly more than females, due to their higher involvement in outdoor activities which increase their chances of getting bitten by sandflies

What are the Risk Factors for Carrion’s Disease? (Predisposing Factors)

The risk factors for Carrion’s Disease may include:

• Living in or traveling to endemic regions in Peru, Colombia, and Ecuador, with increased risk with activities, such as camping, tracking, or sleeping in places which can be potential sandfly breeding or resting sites, including animal farms, trees, caves, etc.
• Blood transfusion received from an asymptomatic carrier or an infected individual
• Transplanted organ received from an asymptomatic or infected individual
• Being born to infected mothers
• Accidental contact with infected blood or discharge from skin lesions (healthcare professionals and laboratory personnel are more at risk)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Carrion’s Disease? (Etiology)

Carrion’s Disease is caused by a bacterium belonging to the genus Bartonella, called Bartonella bacilliformis. It is transmitted through the bites of female sand flies belonging to the genus Lutzomyia.

• Infected individuals are the only known reservoirs of Carrion’s Disease; meaning that the infected individuals are the natural habitat where the bacterium lives, grows, and multiplies
• The disease is transmitted through the bites of female sandflies belonging to the genus Lutzomyia. The female sand fly picks up the bacteria from the blood of an infected individual whom it bites, and then injects the bacteria into the blood of (other) individuals via bites, thereby acting as a vector for the disease

Other possible modes of disease transmission include:

• Blood transfusion
• Organ transplant
• From an infected mother to fetus
• Accidental or intentional inoculation with infected blood or discharge from skin lesions

What are the Signs and Symptoms of Carrion’s Disease?

There are two distinct phases of Carrion’s Disease:

• Acute febrile phase, also known as Oroya Fever that lasts 2-4 weeks
• Eruptive phase, also known as Peruvian Wart/ Verruga Peruana that may last from weeks to months

Acute febrile phase: It is a serious and life-threatening condition, especially in the absence of treatment. It mainly affects previously unexposed individuals whose immune system is new to the infection. This phase is characterized by fever and hemolytic anemia. It may occur 10-210 days after exposure to infection (average incubation period is 61 days) and lasts between 2 and 4 weeks.

The acute febrile phase presents with non-specific signs and symptoms which may include:

• Fever
• Fatigue, malaise
• Decreased appetite
• Headache
• Muscle and joint pains
• Stomach pain
• Nausea and vomiting
• Diarrhea
• Dizziness
• Irritability
• Paleness
• Jaundice
• Somnolence

Eruptive phase: It is a benign condition that occurs in previously exposed individuals and is characterized by skin lesions called Peruvian Warts.

• It may occur weeks to months after the acute hematic phase or may occur without an antecedent acute illness
• The lesions appear as growths in the skin that develop into red-to-purple vascular sores which can bleed on touch
• The skin lesions are usually located on the extremities, trunk, as well as the face. They may also occur in the mouth, nose, or eyes. They last between 3 to 6 months without treatment and heal without leaving scars

How is Carrion’s Disease Diagnosed?

To diagnose Carrion’s Disease, it is important to collect information about the following:

• Clinical data including signs and symptoms, physical examination, and course of the illness including changes in blood chemistry
• History of travel to endemic areas in the Andes Mountains in South America
• History of exposure to sand flies in the endemic regions

Acute phase: The bacteria can be recovered from the blood of all patients during the acute phase. The following tests may be used to confirm the diagnosis:

• Peripheral blood smears: Direct observation of the bacteria inside the red blood cells (RBCs)
• Blood culture: Cultivation of the bacteria from blood
• Serological tests for the detection of antibodies against B. bacilliformis, which may include:
  • Western blot
  • Immunoblot and immunoprecipitation tests
  • Indirect immunofluorescence test (IIF)
• Molecular tests, such as polymerase chain reaction (PCR), to detect the genetic material of the bacteria

Eruptive phase: The suspicious lesions are confirmed by the following tests:

• Histopathological examination: Skin biopsy, where a small piece of the skin lesion is observed under the microscope by a pathologist
• Serological tests
• Culture of Bartonella bacilliformis from skin biopsy samples

This acute phase may resemble other infectious processes such as malaria, typhoid fever, acute brucellosis, viral hepatitis, yellow fever, dengue, leptospirosis, or hematologic malignancies.

There are various skin conditions which can mimic the eruptive phase of Carrion’s Disease. Some of these include:

• Viral eruptions such as chickenpox and molluscum contagiosum
• Bacillary angiomatosis caused by other Bartonella species
• Skin tumors such as hemangioma, pyogenic granuloma, Kaposi sarcoma, etc.
• Other skin diseases such as urticaria, nodular prurigo, psoriasis, etc.
• Leprosy

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Carrion’s Disease?

The acute febrile form of Carrion’s Disease can lead to the following complications which are associated with greater mortality.

• Infectious complications: Carrion’s Disease has been found to cause immunosuppression in the affected individual, meaning that it weakens the immune system. Consequently, the body cannot fight other infections effectively, leading to:
  • Superimposed infections with other pathogens (most commonly Salmonella)
  • Reactivation of pre-existing infections: Toxoplasmosis, tuberculosis, disseminated histoplasmosis, S. aureus sepsis, pneumocstosis, P. vivax malaria, leptospirosis, amebiasis, among others
• Non-infectious complications:
  • Hematological complications: Severe hemolytic anemia and bleeding disorders
  • Cardiovascular complications: Myocarditis/endocarditis (infection of the heart muscles/valves, acute pulmonary edema (fluid accumulation in the lungs), pericardial effusion (fluid accumulation in the cavity around the heart), heart failure, cardiogenic shock, etc.
  • Neurologic complications: Psychomotor agitation, seizures, meningeal irritation, and coma
  • Gastrointestinal complications: Liver enlargement and altered hepatic function, jaundice, ascites (fluid accumulation in the abdominal cavity), dark urine, enlarged spleen, diarrhea, constipation, etc.
  • Multiple organ dysfunction - a highly fatal condition: The illness becomes so severe that it leads to dysfunction of multiple vital organs, causing kidney failure, liver failure, acute respiratory distress syndrome (ARDS), and other complications

Complications in pregnancy: Many severe complications can occur in the fetus and expectant mothers, such as spontaneous abortion, premature delivery, stillbirth, neonatal death, maternal death, and even infection of the newborn through the placenta causing neonatal Oroya Fever.

How is Carrion’s Disease Treated?

• Carrion’s Disease is caused by a bacterial Infection, and hence, antibiotics are the mainstay of treatment. There are several antibiotics available which are effective against Bartonella. The healthcare professional should generally consult an infectious diseases expert regarding the antibiotic options
• The eruptive phase usually requires a long course of antibiotics

Along with antibiotics, the affected individuals with the acute phase may require additional supportive management for the symptoms and complications.

It is important to remember that repeated or long courses of antibiotics can result in the development of antibiotic resistance, meaning that the antibiotics become ineffective in killing the bacteria and treating the infection. Besides, there can be several side effects of taking antibiotics, such as chronic diarrhea and infections, including Clostridium difficile infection. For these reasons, antibiotics should only be taken on the advice of a healthcare professional or an infectious disease expert.

How can Carrion’s Disease be Prevented?

To prevent Bartonella Bacilliformis Infection or Carrion’s Disease, the following measures can be undertaken:

• Controlling the adult population of the sandfly by using physical and chemical methods of vector control
• Avoiding/limiting travel to the endemic regions of Carrion’s Disease, especially to certain isolated, rural communities in Peru, Colombia, and Ecuador
• Individuals, such as tourists and workers, who visit the endemic areas should take steps to avoid sandfly bites by considering the following measures:
  • Applying suitable insect repellents on skin
  • Wearing long-sleeved shirts and long pants
  • Avoiding/limiting outdoor activities during the periods when sand flies are most active (in the evenings after 5)
  • Using mosquito nets while sleeping
  • Avoiding camping or sleeping in abandoned houses
  • Avoiding sleeping in places that can be potential sandfly breeding or resting sites, such as animal farms, beneath trees, and inside caves

What is the Prognosis of Carrion’s Disease? (Outcomes/Resolutions)

• In the absence of treatment, the acute phase of Carrion’s Disease is a severe condition with a mortality rate as high as 88%. However, with appropriate antibiotic therapy, the mortality rates have decreased by about ten times. Mortality can be further decreased with early diagnosis, treatment, and provision of advanced healthcare facilities
• When treated appropriately, most of the individuals with the acute phase recover fully without any long-term complications. A small proportion (about 5%) develop the eruptive phase after some weeks or months of the acute phase
• The lesions of the eruptive phase (Verruga Peruana) heal without scars in most individuals. However, they can last between 3 to 6 months in the absence of suitable treatment
• There is a small possibility of recurrence of both the acute phase as well as chronic phase even after treatment of the initial infection

Additional and Relevant Useful Information for Carrion’s Disease:

Carrion’s Disease is named as a tribute to Daniel Alcides Carrion, a Peruvian medical student, who sacrificed his life to establish that Oroya Fever and Verruga Peruana were caused by the same pathogen. He inoculated himself with the discharge from a patient with Peruvian Wart; he subsequently developed the acute febrile hemolytic phase which took his life after a few weeks. The organism Bartonella bacilliformis is named after another Peruvian doctor, Alberto Barton, who described the organism that causes Oroya Fever.