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Infectious Disease -Bartonellosis (Oroya Fever/Verruga Peruana)
A disease caused by Bartonella bacilliformis, transmitted by the Phlebotomus sandfly, occurring in endemic regions in two distinct manifestations:
• Nonimmune individuals exhibit an acute febrile sickness accompanied by severe anemia (Oroya fever). • Following a variable duration post-resolution, a persistent, benign cutaneous manifestation may arise, marked by angioproliferative skin lesions (verruga peruana). The former exhibit a notable resemblance to lesions of bacillary angiomatosis, induced by Bartonella henselae and Bartonella quintana.
EPIDEMIOLOGY
Frequency
The disease is only confined to the valleys of the Andes River at elevations ranging from 600 to 2,500 meters in Peru, Ecuador, and Colombia.
• The majority of Oroya fever cases arise in tourists or visitors who
are immunologically inexperienced. The majority of verruga peruana cases occur within the indigenous community, with infrequent instances identified in the United States.
RISK FACTORS
Life in endemic regions and exposure to the sandfly vector GENERAL PREVENTION
Prevention necessitates the regulation of the sandfly vector: Application of dichlorodiphenyltrichloroethane (DDT) on both the interiors and exteriors of residences, utilization of insect repellents, and implementation of bed netting.
PATHOPHYSIOLOGY • Bartonella spp. infiltrate erythrocytes and endothelial cells. • They proliferate within intracellular vacuoles in the erythrocytes. The latter are subsequently engulfed and eliminated by the reticuloendothelial system.
ETIOLOGY • B. bacilliformis is a diminutive, gram-negative bacillus belonging to the class Proteobacteria, closely associated with B. quintana.
• It is spread through an arthropod vector, specifically the sandfly (Phlebotomus).
DIAGNOSTIC HISTORY
The incubation period for Oroya fever is approximately 3 weeks, with a maximum duration of 100 days.
The development of symptoms, primarily due to elevated temperature and severe anemia, may be either acute or subacute.
• Infectious problems arise from temporary immunosuppression.
The acute phase is followed by the convalescent period.
• Verruca skin lesions (nodules) manifest in clusters during a period of 1 to 2 months, after a variable interval after the remission of Oroya fever.
Acute manifestation (Oroya Fever)
• Subacute presentation (mild fever, malaise, cephalalgia, anorexia).
• Abrupt onset (elevated temperature, chills, sweating, cephalalgia, and alterations in cognitive function, succeeded by the rapid emergence of severe anemia).
• Myalgia and arthralgia.
• Dyspnea and angina; the patient may get the sensation that
The heart pulse is conveyed to the head and ears. • Anasarca serves as an indicator of unfavorable prognosis.
• Insomnia, delirium, diminished awareness, coma.
• In the ensuing convalescent (critical) phase, fever abates and anemia symptoms ameliorate.
PHYSICAL EXAMINATION
Oroya Fever • Elevated temperature • Indicators of severe anemia
• Generalized, nontender lymphadenopathy • Splenomegaly is uncommon; if observed, it may suggest an additional concomitant infection
• Thrombocytopenic purpura
Peruvian Wart
Miliary lesions comprise many papular, erythematous, round lesions measuring 1–4 mm, often accompanied by pruritus (1).
Nodular lesions, typically located on the skin and subcutaneous tissues of exposed body areas, may also involve mucous membranes and interior organs.
Mular lesions generally exceed 5 mm in diameter.
Characterized by erythema and a propensity to hemorrhage quickly.
• Lesions at different stages of development may be simultaneously present.
• Local tenderness is absent unless the patient has a secondary infection.
DIAGNOSTIC TESTS AND INTERPRETATION Laboratory
In the acute phase, diagnosis is established through a positive culture (blood or bone marrow) or the identification of many organisms attached to red blood cells in peripheral thin-film blood smears (utilizing Giemsa or Wright stain). The bacterial count decreases sharply during convalescence.
Peripheral blood smears may reveal macrocytosis, poikilocytosis, Howell–Jolly bodies, nucleated red blood cells, and immature myeloid cells. The leukocyte differential exhibits a leftward shift, but the total count may remain within normal limits.
• Severe anemia; negative Coombs' test
In the subacute form, initial peripheral blood smears may yield negative results; diagnosis can be established through positive blood cultures.
Diagnosis of the chronic type can be achieved through the identification of the causal agent in culture.
Samples from cutaneous lesions and bone marrow cultures. • Blood cultures may yield positive results in asymptomatic patients. • Serological assays (ELISA, indirect fluorescent antibody, western immunoblot) can assist in diagnosis (2,3).
Pathological Findings: Skin biopsy, bone marrow aspiration, and biopsy specimens from further afflicted organs are utilized.
Enhanced angiogenesis, Rocha-Lima inclusions within endothelial cells
The polymerase chain reaction (PCR) for the detection of B. bacilliformis is currently in development.
DIFFERENTIAL DIAGNOSIS
• The acute phase can be readily distinguished from other endemic febrile conditions (e.g., malaria, typhoid fever, leptospirosis) through the analysis of peripheral blood smears and bacterial cultures. • Verruga peruana lesions bear resemblance to those of bacillary angiomatosis, Kaposi’s sarcoma, lymphoproliferative disorders, and other neoplasms. The primary diagnostic indicator is epidemiology.
THERAPEUTIC PHARMACEUTICAL
Oroya fever: Administer chloramphenicol (500 mg orally or intravenously every 6 hours) in conjunction with a secondary antibiotic, preferably a beta-lactam (such as penicillin), for a duration of 14 days (AII) (4).
Chloramphenicol is effective against salmonellosis, the prevalent secondary infection. The suggestion to incorporate a beta-lactam stems from the understanding that chloramphenicol alone is not dependable.
• Verruga peruana: – Administer Rifampin at a dosage of 10 mg/kg daily, not exceeding 600 mg daily, for a duration of 10–14 days (AII) orally (4). Second Line • Oroya fever: – Administer Doxycycline 100 mg orally twice daily for 14 days
The bacteria exhibits a prevalent resistance to ciprofloxacin.
Consequently, quinolones are not advised. • Verruga peruana: – Administer streptomycin at a dosage of 15–20 mg/kg intramuscularly on a daily basis for a duration of 10 days (AII)
SUPPLEMENTARY THERAPY
Comprehensive Strategies
Supportive and symptomatic treatment is essential in the acute form; employ blood transfusion to ameliorate anemia.
OPERATIVE INTERVENTIONS/ADDITIONAL PROCEDURES
Extensive and secondarily infected cutaneous nodules may require surgical removal.
INPATIENT CONSIDERATIONS
Criteria for Admission
The suitable health care environment is inpatient for acute conditions and outpatient for chronic conditions.
CONTINUING MANAGEMENT POST-TREATMENT GUIDELINES
• Assess hydration levels and perform a complete blood count during the acute phase.
Monitor indicators of further infections: Splenomegaly, recurrent fever accompanied by leukocytosis throughout the convalescent phase, and diarrhea.
Observe verruca lesions for indications of subsequent infections.
PROGNOSIS • Untreated Oroya fever may result in mortality rates of 50–88%.
• Fever resolves within 24 hours following suitable antibiotic therapy, however bacteremia may endure for extended durations.
COMPLICATIONS
• Verruca lesions exhibit a varied response to antimicrobial therapy.
• Secondary bacterial infections, such as salmonellosis and other intestinal infections, malaria, and tuberculosis, are prevalent (45%) during the convalescent phase of Oroya fever. • Verruga lesions may become secondarily infected, leading to pustulation, ulceration, and hemorrhage.
A disease caused by Bartonella bacilliformis, transmitted by the Phlebotomus sandfly, occurring in endemic regions in two distinct manifestations:
• Nonimmune individuals exhibit an acute febrile sickness accompanied by severe anemia (Oroya fever). • Following a variable duration post-resolution, a persistent, benign cutaneous manifestation may arise, marked by angioproliferative skin lesions (verruga peruana). The former exhibit a notable resemblance to lesions of bacillary angiomatosis, induced by Bartonella henselae and Bartonella quintana.
EPIDEMIOLOGY
Frequency
The disease is only confined to the valleys of the Andes River at elevations ranging from 600 to 2,500 meters in Peru, Ecuador, and Colombia.
• The majority of Oroya fever cases arise in tourists or visitors who
are immunologically inexperienced. The majority of verruga peruana cases occur within the indigenous community, with infrequent instances identified in the United States.
RISK FACTORS
Life in endemic regions and exposure to the sandfly vector GENERAL PREVENTION
Prevention necessitates the regulation of the sandfly vector: Application of dichlorodiphenyltrichloroethane (DDT) on both the interiors and exteriors of residences, utilization of insect repellents, and implementation of bed netting.
PATHOPHYSIOLOGY • Bartonella spp. infiltrate erythrocytes and endothelial cells. • They proliferate within intracellular vacuoles in the erythrocytes. The latter are subsequently engulfed and eliminated by the reticuloendothelial system.
ETIOLOGY • B. bacilliformis is a diminutive, gram-negative bacillus belonging to the class Proteobacteria, closely associated with B. quintana.
• It is spread through an arthropod vector, specifically the sandfly (Phlebotomus).
DIAGNOSTIC HISTORY
The incubation period for Oroya fever is approximately 3 weeks, with a maximum duration of 100 days.
The development of symptoms, primarily due to elevated temperature and severe anemia, may be either acute or subacute.
• Infectious problems arise from temporary immunosuppression.
The acute phase is followed by the convalescent period.
• Verruca skin lesions (nodules) manifest in clusters during a period of 1 to 2 months, after a variable interval after the remission of Oroya fever.
Acute manifestation (Oroya Fever)
• Subacute presentation (mild fever, malaise, cephalalgia, anorexia).
• Abrupt onset (elevated temperature, chills, sweating, cephalalgia, and alterations in cognitive function, succeeded by the rapid emergence of severe anemia).
• Myalgia and arthralgia.
• Dyspnea and angina; the patient may get the sensation that
The heart pulse is conveyed to the head and ears. • Anasarca serves as an indicator of unfavorable prognosis.
• Insomnia, delirium, diminished awareness, coma.
• In the ensuing convalescent (critical) phase, fever abates and anemia symptoms ameliorate.
PHYSICAL EXAMINATION
Oroya Fever • Elevated temperature • Indicators of severe anemia
• Generalized, nontender lymphadenopathy • Splenomegaly is uncommon; if observed, it may suggest an additional concomitant infection
• Thrombocytopenic purpura
Peruvian Wart
Miliary lesions comprise many papular, erythematous, round lesions measuring 1–4 mm, often accompanied by pruritus (1).
Nodular lesions, typically located on the skin and subcutaneous tissues of exposed body areas, may also involve mucous membranes and interior organs.
Mular lesions generally exceed 5 mm in diameter.
Characterized by erythema and a propensity to hemorrhage quickly.
• Lesions at different stages of development may be simultaneously present.
• Local tenderness is absent unless the patient has a secondary infection.
DIAGNOSTIC TESTS AND INTERPRETATION Laboratory
In the acute phase, diagnosis is established through a positive culture (blood or bone marrow) or the identification of many organisms attached to red blood cells in peripheral thin-film blood smears (utilizing Giemsa or Wright stain). The bacterial count decreases sharply during convalescence.
Peripheral blood smears may reveal macrocytosis, poikilocytosis, Howell–Jolly bodies, nucleated red blood cells, and immature myeloid cells. The leukocyte differential exhibits a leftward shift, but the total count may remain within normal limits.
• Severe anemia; negative Coombs' test
In the subacute form, initial peripheral blood smears may yield negative results; diagnosis can be established through positive blood cultures.
Diagnosis of the chronic type can be achieved through the identification of the causal agent in culture.
Samples from cutaneous lesions and bone marrow cultures. • Blood cultures may yield positive results in asymptomatic patients. • Serological assays (ELISA, indirect fluorescent antibody, western immunoblot) can assist in diagnosis (2,3).
Pathological Findings: Skin biopsy, bone marrow aspiration, and biopsy specimens from further afflicted organs are utilized.
Enhanced angiogenesis, Rocha-Lima inclusions within endothelial cells
The polymerase chain reaction (PCR) for the detection of B. bacilliformis is currently in development.
DIFFERENTIAL DIAGNOSIS
• The acute phase can be readily distinguished from other endemic febrile conditions (e.g., malaria, typhoid fever, leptospirosis) through the analysis of peripheral blood smears and bacterial cultures. • Verruga peruana lesions bear resemblance to those of bacillary angiomatosis, Kaposi’s sarcoma, lymphoproliferative disorders, and other neoplasms. The primary diagnostic indicator is epidemiology.
THERAPEUTIC PHARMACEUTICAL
Oroya fever: Administer chloramphenicol (500 mg orally or intravenously every 6 hours) in conjunction with a secondary antibiotic, preferably a beta-lactam (such as penicillin), for a duration of 14 days (AII) (4).
Chloramphenicol is effective against salmonellosis, the prevalent secondary infection. The suggestion to incorporate a beta-lactam stems from the understanding that chloramphenicol alone is not dependable.
• Verruga peruana: – Administer Rifampin at a dosage of 10 mg/kg daily, not exceeding 600 mg daily, for a duration of 10–14 days (AII) orally (4). Second Line • Oroya fever: – Administer Doxycycline 100 mg orally twice daily for 14 days
The bacteria exhibits a prevalent resistance to ciprofloxacin.
Consequently, quinolones are not advised. • Verruga peruana: – Administer streptomycin at a dosage of 15–20 mg/kg intramuscularly on a daily basis for a duration of 10 days (AII)
SUPPLEMENTARY THERAPY
Comprehensive Strategies
Supportive and symptomatic treatment is essential in the acute form; employ blood transfusion to ameliorate anemia.
OPERATIVE INTERVENTIONS/ADDITIONAL PROCEDURES
Extensive and secondarily infected cutaneous nodules may require surgical removal.
INPATIENT CONSIDERATIONS
Criteria for Admission
The suitable health care environment is inpatient for acute conditions and outpatient for chronic conditions.
CONTINUING MANAGEMENT POST-TREATMENT GUIDELINES
• Assess hydration levels and perform a complete blood count during the acute phase.
Monitor indicators of further infections: Splenomegaly, recurrent fever accompanied by leukocytosis throughout the convalescent phase, and diarrhea.
Observe verruca lesions for indications of subsequent infections.
PROGNOSIS • Untreated Oroya fever may result in mortality rates of 50–88%.
• Fever resolves within 24 hours following suitable antibiotic therapy, however bacteremia may endure for extended durations.
COMPLICATIONS
• Verruca lesions exhibit a varied response to antimicrobial therapy.
• Secondary bacterial infections, such as salmonellosis and other intestinal infections, malaria, and tuberculosis, are prevalent (45%) during the convalescent phase of Oroya fever. • Verruga lesions may become secondarily infected, leading to pustulation, ulceration, and hemorrhage.
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