| Bartonellosis | |
|---|---|
| Specialty | Infectious diseases  |
Bartonellosis is aninfectious disease caused bybacteria of thegenusBartonella.[1]Bartonella species cause diseases such asCarrión's disease,trench fever,cat-scratch disease,bacillary angiomatosis,peliosis hepatis, chronicbacteremia,endocarditis, chroniclymphadenopathy, and neurological disorders.[2]
Patients can develop two clinical phases: anacute septic phase and achronic eruptive phase associated withskin lesions.[3] In the acute phase (also known asOroya fever orfiebre de la Oroya),B. bacilliformis infection is a sudden, potentially life-threatening infection associated with highfever and decreased levels of circulatingred blood cells (i.e.,hemolytic anemia) and transient immunosuppression.B. bacilliformis is considered the most deadly species to date, with a death rate of up to 90% during the acute phase, which typically lasts two to four weeks.Peripheral blood smears show anisomacrocytosis with manybacilli adherent tored blood cells.Thrombocytopenia is also seen and can be very severe. Neurologic manifestations (neurobartonellosis) are altered mental status, agitation, or even coma, ataxia, spinalmeningitis, orparalysis. It is seen in 20% of patients with acute infection, in which theprognosis is very guarded with about 50% mortality. The most feared complication is an overwhelming infection mainly by Enterobacteriaceae, particularlySalmonella (bothS. typhi and S.non-typhi, as well as reactivation oftoxoplasmosis and other opportunistic infections.[citation needed]
The chronic manifestation consists of abenign skin eruption with raised, reddish-purplenodules (angiomatous tumours). The bacterium can be seen microscopically if a skin biopsy issilver stained (theWarthin–Starry method).[citation needed]
Cat-scratch disease is due to an infection byB. henselae. It manifests as gradual regionallymph nodes enlargement (axilla,groin,neck) which may last 2–3 months or longer, and a distalscratch and/or red-brown skinpapule (not always seen at the time of the disease). The enlarged lymph node is painful and tender. The lymph nodes may suppurate, and some patients remain afebrile or asymptomatic. Other presentations include fever (particularly in children), Parinaud's oculoglandular syndrome,encephalopathy, and neuroretinitis.[4][5]
B. henselae can be associated with bacteremia, bacillary angiomatosis, and peliosis hepatis inHIV patients, and bacteremia and endocarditis in immunocompetent and immunocompromised patients.[6] Symptoms may include fatigue, headaches, fever, memory loss, disorientation, insomnia, and loss of coordination. The bacteria block the normal immune response by suppressing the NF-κB apoptosis pathway.[7] Disease progression may be accelerated if the host is subsequently infected by an immune-suppressing virus such as Epstein-Barr.[citation needed]
B. henselae andB. quintana can cause bacillary angiomatosis, avascular proliferative disease involving mainly the skin, and other organs. The disease was first described in human immunodeficiency virus (HIV) patients andorgan transplant recipients.[8] Severe, progressive and disseminated disease may occur in HIV patients.[9] Differential diagnoses includeKaposi's sarcoma,pyogenicgranuloma,hemangioma,verruga peruana, and subcutaneous tumors. Lesions can affectbone marrow,liver,spleen, orlymph nodes.[citation needed]
B. henselae is the etiologic agent for peliosis hepatis, which is defined as a vascular proliferation ofsinusoid hepaticcapillaries resulting in blood-filled spaces in the liver in HIV patients and organ transplant recipients. Peliosis hepatis can be associated with peliosis of the spleen, as well as bacillary angiomatosis of the skin in HIV patients.[10]
Trench fever, also known as five-day fever or quintan fever, is the initial manifestation ofB. quintana infection. Clinical manifestations range from asymptomatic infection to severe illness. Classical presentations include a febrile illness of acute onset,headache,dizziness, andshin pain. Chronic infection manifestations include attacks of fever and aching in some cases and persistent bacteremia insoldiers andhomeless people.[11]
Members of the genusBartonella are facultative intracellular bacteria, alpha 2 subgroupPseudomonadota. The genus comprises:
| Bartonella species | Reservoir | Disease |
|---|---|---|
| Bartonella bacilliformis | human | Carrion's disease /verruga Peruana |
| Bartonella quintana | human | Trench fever, bacteremia, bacillary angiomatosis, endocarditis |
| Bartonella henselae | cats | Cat-scratch disease, bacillary angiomatosis, bacteremia, endocarditis, encephalitis, meningitis |
| Bartonella elizabethae | rats | Endocarditis |
| Bartonella grahamii | Retinitis | |
| Bartonella vinsoni | dogs | Endocarditis, bacteremia |
| Bartonella washonsis | rodents | Myocarditis |
| Bartonella clarridgiae | cats | Bacteremia |
| Bartonella rochalimae | human | Carrion's disease-like syndrome |
In mammals, eachBartonella species is highly adapted to its reservoir host as the result of intracellular parasitism and can persist in the host's bloodstream. Intraerythrocytic parasitism is only observed in the acute phase ofCarrion's disease.Bartonella species also have a tropism for endothelial cells, observed in the chronic phase of Carrion's disease (also known asverruga Peruana) andbacillary angiomatosis.Pathological response can vary with the immune status of the host. Infection withB. henselae can result in a focal suppurative reaction (CSD in immunocompetent patients), a multifocal angioproliferative response (bacillary angiomatosis in immunocompromised patients),endocarditis, ormeningitis.[citation needed]
There are several methods used for diagnosingBartonella infection includingmicroscopy,serology, andPCR.[12]Microscopy of blood smears is used to diagnose Carrión's disease (B. bacilliformis), however for otherBartonella species, microscopy andsilver staining are insensitive, not highly specific, and cannot differentiate species.[12][13] The CDC does not recommend lymph node aspiration for diagnostic purposes.[12]
IFA (immunofluorescenceantibody assay) testing for the presence of antibodies in serum is used to diagnoseB. henselae infection at the acute onset of Cat Scratch Disease symptoms, followed by PCR to confirm infecting species.[13][14][15] IFA can generally be used to confirm a diagnosis ofBartonella infection but is limited by antibody cross-reactivity with other bacteria species[12][13] which can cause a false positive, and antigen variability which can result in false negatives.[13][16]
Bartonella spp. often evade an immune response, thus antibodies may not be detected even concurrent with an infection, resulting in an IFA false negative rate of up to 83% in chronically infected patients when other test results (e.g. organism isolation or PCR) are positive.[13][14][15][16] IFA sensitivity may range from 14 to 100%,[13] causing discrepancies between PCR and serology test results.[16] Positive IFA results do not distinguish between current infection and prior exposure.[citation needed]
ELISA (enzyme-linked immunosorbent assay) is another method that has been used to detect Bartonella, but it has a low sensitivity (17-35%).[13]Western blot for protein detection of Bartonella-associated proteins has also been reported, but this method does not show clear immunoreactive profiles.[13]
The CDC states thatPCR testing from a single blood draw is not sufficiently sensitive forB.henselae testing,[12] and can result in high false negative rates[16] due to a small sample volume and levels below the limit of molecular detection.[13]
Bartonella spp. are fastidious, slow-growing bacteria that are difficult to grow using traditional solid agar plate culture methods due to complex nutritional requirements and potentially a low number of circulating bacteria.[12][16][17][18][19] This conventional method of culturingBartonella spp. from blood inoculates plated directly onto solid agar plates requires an extended incubation period of 21 days due to the slow growth rate.[12][16][20]
Bartonella growth rates improve when cultured in an enrichment inoculation step in a liquid insect-based medium[17][20][21] such asBartonella Alphaproteobacteria Growth Medium (BAPGM)[16] or Schneider's Drosophila-based insect powder medium.[20][21] Several studies have optimized the growing conditions ofBartonella spp. cultures in these liquid media, with no change in bacterial protein expressions or host interactionsin vitro.[20][21] Insect-based liquid media supports the growth and co-culturing of at least sevenBartonella species,[13][16][20][21] reduces bacterial culturing time and facilitates PCR detection and isolation ofBartonella spp. from animal and patient samples.[13][16][18] Research shows that DNA may be detected following direct extraction from blood samples and become negative following enrichment culture, thus PCR is recommended after direct sample extraction and also following incubation in enrichment culture.[16] Several studies have successfully optimized sensitivity and specificity by using PCR amplification (pre-enrichment PCR) and enrichment culturing of blood draw samples, followed by PCR (post-enrichment PCR) and DNA sequence identification.[18][22]
AsBartonella spp. infect at low levels and cycle between blood and tissues,[17] multiple blood draws over time may be necessary to detect infection.[23]
Treatment of infections caused byBartonella species include:[24][25]
| Disease | Adults | Children |
|---|---|---|
| Cat-scratch disease | Azithromycin + Rifampin | Unknown |
| Retinitis | Doxycycline + rifampin | unknown |
| Trench fever or chronic bacteremia by B. quintana | Doxycycline + gentamicin | unknown |
| Bacillary angiomatosis | Erythromycin or doxycycline | Erythromycin |
| Peliosis hepatis | Erythromycin or doxycycline | Erythromycin |
| Endocarditis | Doxycycline + gentamicin + rifampin or ceftriaxone + gentamicin | |
| Carrión's disease (acute phase) | Ciprofloxacin or chloramphenicol | Chloramphenicol + beta-lactam |
| Carrión's disease (chronic phase) | Rifampin or macrolides | Rifampin or macrolides |
Some authorities recommend the use ofazithromycin.[26]
Carrión's disease, or Oroya fever or Peruvian wart is a rareinfectious disease found only inPeru,Ecuador, andColombia.[27] It isendemic in some areas ofPeru,[28] is caused by infection with thebacteriumBartonella bacilliformis, and transmitted bysandflies ofgenusLutzomyia.
Cat scratch disease occurs worldwide. Cats are the main reservoir ofBartonella henselae,[29] and the bacterium is transmitted to cats by the cat fleaCtenocephalides felis.[30] Infection in cats is very common with a prevalence estimated between 40 and 60%, younger cats being more commonly infective. Cats usually become immune to the infection, while dogs may be very symptomatic. Humans may also acquire it through flea or tick bites from infected dogs, cats, coyotes, and foxes.[citation needed]
Trench fever, produced byBartonella quintana infection, is transmitted by thehuman body lousePediculus humanus corporis. Humans are the only known reservoir.[31] Thorough washing of clothing may help to interrupt the transmission of infection.[citation needed]
A possible role for ticks in the transmission ofBartonella species remains to be elucidated; in November 2011,Bartonella rochalimae,B. quintana, andB. elizabethae DNA was first reported inRhipicephalus sanguineus andDermacentor nitens ticks in Peru.[32]
The disease was named after medical studentDaniel Alcides Carrión fromCerro de Pasco,Peru. Carrión described the disease after being inoculated at his request with the pus of a skin lesion from patient Carmen Paredes in 1885 by Doctor Evaristo M. Chávez, a close friend and coworker inDos de Mayo National Hospital. Carrión developed the disease three weeks after the inoculation and kept a meticulous record of clinical symptoms and signs until the disease rendered him incapable of the task and he died at age 28 several weeks later—October 5, 1885. Carrión proved that Oroya fever andverruga peruana were two stages of the same disease and not two different diseases as was thought at the time. His work did not result in a cure immediately, but his research started the process. Peru has named October 5 as "Peruvian Medicine Day" in his honor.[citation needed]
Peruvian microbiologistAlberto Barton discovered the causative bacterium in 1905, but his results were not published until 1909. Barton originally identified them as "endoglobular" structures, bacteria living inside red blood cells. Until 1993, thegenusBartonella, within the family Bartonellaceae, contained only one species; 23 are now identified.[33]
In 1988, Englishet al.[34] isolated and cultured a bacterium that was namedAfipia felis in 1992 after the team at theArmed Forces Institute of Pathology that discovered it. This agent was considered the cause of cat-scratch Disease (CSD) but further studies failed to support this conclusion. Serologic studies associated CSD withBartonella henselae, reported in 1992. In 1993, Dolan[35] isolatedRochalimae henselae (now calledBartonella henselae) from lymph nodes of patients with CSD.
Bartonella spp. are commonly treated with antibiotics including azithromycin, based on a single small randomized clinical trial. Treatment may take up to one year to eliminate the disease.CSD often resolves spontaneously without treatment.[36]
Detailed descriptions of the disease were reported in soldiers during theFirst World War. It is also known as five-day fever, quintan fever, Wolhinie fever, and urban trench fever because it occurs in homeless people and alcoholics .[37]