Version May 2024
INTRODUCTION — Bartonella quintana is a species of Bartonella, which historically caused "trench fever" and more recently has been associated with a variety of infections including bacteremia, endocarditis, and bacillary angiomatosis.
The clinical features, diagnosis, and treatment of B. quintana infection will be reviewed here. Endocarditis due to Bartonella spp, Bartonella infection in people with HIV (eg, bacillary angiomatosis, peliosis hepatis), and bartonella infections caused by species other than B. quintana are discussed separately. (See "Endocarditis caused by Bartonella" and "Bartonella infections in people with HIV" and "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease" and "Treatment of cat scratch disease" and "South American bartonellosis: Oroya fever and verruga peruana".)
MICROBIOLOGY — B. quintana is a small, fastidious, gram-negative rod formerly known as Rochalimaea quintana, Rickettsia quintana, Rickettsia weigli, Rickettsia volhynia, and Rickettsia pediculi [1].
Other Bartonella spp that cause human disease include B. henselae and B. bacilliformis. Further details regarding those species and the general microbiology of Bartonella spp are found separately. (See "Basic biology of Bartonella species".)
EPIDEMIOLOGY
History — During World War I, B. quintana infection emerged as a major source of morbidity among soldiers and was commonly referred to as trench fever. More than a million soldiers developed trench fever, and military physicians established the War Office Trench Fever Investigation Commission [2,3]. This group identified the causative organism and determined that the human body louse was the vector for the infectious pathogen. During World War II, a significant, but less extensive, trench fever epidemic occurred.
Subsequently, endemic and sporadic outbreaks of trench fever were reported in the middle part of the 20th century in multiple regions of the world, including Ethiopia (1946), Poland (1949), Mexico (1954), USSR (1960), and Tunisia (1961) [4].
Geography — B. quintana has a worldwide distribution, although clinically significant infections are uncommon. Since the 1990s, cases have been sporadically reported in the United States, Europe, Russia, Brazil, and East Africa [5-13].
Risk factors — Contemporary B. quintana infections occur in situations that foster very close contact of humans, particularly environments with poor hygienic conditions where lice infestations can occur. Outbreaks have been reported in individuals experiencing homelessness, living in refugee camps, and incarcerated in crowded jails or prisons [5-7,11,14-24]. Those with HIV, alcohol use disorder, or injection drug use may be particularly prone to infection [5,7,11,15,19,25,26].
Determining the overall prevalence of B. quintana infection in at-risk populations is challenging, in part because persons with infection may be asymptomatic and may not seek health care. Serologic antibody studies of impoverished or homeless populations in the United States and France have found that 8 to 53 percent had prior B. quintana infection compared with 0 to 2 percent of healthy blood donors; studies from other locales have found similar results [6,15-19,26]. Blood culture screening studies have found rates of B. quintana bacteremia ranging from 5 to 14 percent among populations of individuals who are homeless, compared with 0 percent of sex- and age-matched controls [6,18].
Transmission — Humans are the main host for B. quintana, and the primary route of spread is via exposure to infected lice [1,3,6,11,13,20-22,24,26]. Available data suggest the body louse (P. humanus var corporis) is the predominant vector, although the head louse (Pediculus humanus var capitis) and pubic louse (P. humanus var pubis) can also potentially transmit B. quintana.
Lice become carriers of the organism by feeding on an infected human or other animal reservoir. Noninfected humans acquire the organism from inoculation of infected louse feces into abraded skin or conjunctiva. An infected louse can excrete millions of B. quintana organisms in its feces per day [24,27]. The bite of the louse does not appear to transmit infection to humans [3,24,28].
Besides lice, other potential vectors have been proposed, but data supporting their role in transmission to humans are scarce. For example, cats are not natural hosts for B. quintana, but the organism has been isolated from cat fleas and cat dental pulp; rare cases of infection have been reported following exposure to cats, including cat scratches [1,5,29-31]. In a study from 1939, ticks were reported to harbor the organism after feeding on infected humans [32]. Bed bugs (Cimex lectularius) can acquire B. quintana and release the bacteria in their feces [33].
Although humans are thought to be the main host for B. quintana, nonhuman primates, specifically macaques, also serve as natural hosts for the organism [34]. Data suggest that B. quintana disease in humans may have originated zoonotically from spillover of subsets of macaque B. quintana strains into human populations.
CLINICAL MANIFESTATIONS — Contemporary infections caused by B. quintana encompass a number of distinct syndromes [35].
Incubation period — The incubation period ranges from 5 to 20 days, based on controlled studies of human volunteers inoculated with infected louse feces [36]. In the original reports from World War I, the incubation period was 7 to 8 days [3].
Febrile illness — Febrile illness can have variable presentations, ranging from a mild self-limited influenza-like illness to chronic, debilitating disease [2,32,36]. Typical symptoms and signs include malaise, fever, headache, dizziness, bone pain (particularly of the shins), splenomegaly, nausea, vomiting, and, in some instances, a macular truncal rash [3].
Three major fever patterns have been identified [2,36]:
●Three to five recurrent febrile episodes, each lasting four to five days, with asymptomatic intervals of four to five days between each episode. This is classic "trench fever" and was the most frequent form of illness during the early half of the twentieth century, including World War I. It was termed "quintan fever" or "pentan fever" because of the recurring five-day attacks. Experts today presume that those patients with classic trench fever had bacteremia, but this is unproven because patients during those times did not get blood cultures. In modern times, this form of illness (ie, classic trench fever) is uncommon.
●A single febrile episode lasting four to five days.
●Persistent fever lasting two to six weeks.
Chronic bacteremia — After resolution of febrile events, prolonged asymptomatic bacteremia can persist for weeks to months. Patients may have persistently positive blood cultures, or bacteremia may be intermittent. In some outbreak situations, positive cultures are found in individuals who have no recollection of prior febrile or systemic illness [5,6,25,29,37].
Endocarditis — Data suggest that 20 to 43 percent of patients with B. quintana bacteremia have endocarditis [5,6,25]. The organism is also a significant cause of culture-negative endocarditis, causing up to 15 percent of culture-negative endocarditis cases in some series [9,10,38]. B. quintana is a more frequent cause of endocarditis than B. henselae and may be associated with more frequent systemic emboli [7,8,38,39].
Clinical manifestations of bartonella endocarditis match those of bacteremia (eg, malaise, fever). In addition, a heart murmur, weight loss, or signs of systemic emboli (eg, stroke, skin findings) may be present. A detailed description of bartonella endocarditis is found elsewhere. (See "Endocarditis caused by Bartonella".)
Infections in people with HIV — In individuals with advanced HIV (eg, CD4 <100 cells/microL), B. quintana infections were first described in the early 1990s, particularly among those experiencing homelessness or crowded living situations where lice infestations can occur [12,40].
Patients with any stage of HIV can present with the various forms of B. quintana illness (eg, febrile illness, chronic bacteremia, endocarditis) [11,19]. In addition, patients with advanced HIV can have unique presentations (ie, bacillary angiomatosis and bacillary peliosis hepatitis), as described below. (See 'Clinical manifestations' above and 'Bacillary angiomatosis' below and 'Bacillary peliosis hepatitis' below.)
Bacillary angiomatosis — This syndrome occurs in patients with advanced HIV who have CD4 counts less than 100 cells/microL. It is caused by either B. quintana or B. henselae. Affected patients present with vascular lesions that most frequently involve the skin but can affect other organs, such as bone and lymph nodes (picture 1 and picture 2) [12]. Patients with infection due to B. quintana may be more likely to have lytic bone lesions than patients with B. henselae [11]. Further details are found separately. (See "Bartonella infections in people with HIV", section on 'Bacillary angiomatosis'.)
Bacillary peliosis hepatitis — Like bacillary angiomatosis, this syndrome occurs in patients with advanced HIV-related immunosuppression (CD4 <100 cells/microL). Patients with this syndrome present with abdominal pain and hepatosplenomegaly, with or without systemic symptoms (eg, fever); laboratory tests reveal elevated alkaline phosphatase. Data suggest that B. quintana is less likely to cause this syndrome than B. henselae [11,41]. Detailed discussion is found separately. (See "Bartonella infections in people with HIV", section on 'Bacillary peliosis hepatis and splenitis'.)
DIAGNOSIS
When to suspect B. quintana infection — In general, B. quintana infection should be suspected in patients with an unexplained systemic febrile illness or culture-negative endocarditis, especially if the person is experiencing homelessness or living in crowded living conditions where lice infestations can occur. (See 'Clinical manifestations' above.)
Among patients with advanced HIV (eg, CD4 <100 cells/microL), symptoms and signs of bacillary angiomatosis (eg, angiomatous vascular cutaneous lesions, lytic bone lesion) or bacillary peliosis hepatis (eg, abdominal pain, hepatosplenomegaly, elevated alkaline phosphatase, hypodense liver lesions on imaging) should increase suspicion for either B. quintana or B. henselae infection. (See 'Bacillary angiomatosis' above and 'Bacillary peliosis hepatitis' above and "Bartonella infections in people with HIV".)
Confirming the diagnosis — The diagnosis of B. quintana infection is challenging. A definitive diagnosis of Bartonella infection is made by identifying the organism from culture or polymerase chain reaction (PCR) of blood or tissue. However, because culturing Bartonella is difficult, the diagnosis is often made based on positive serologic antibody tests (IgM or IgG); such serologic tests provide supportive, but not definitive, evidence of infection.
When an infection due to B. quintana is suspected, we send blood samples for the following tests:
●Two sets of blood cultures. We ask the microbiology lab to incubate the cultures for at least 28 days. In a case series of 14 infected individuals in the United States, the average time to culture positivity was 12 days [25].
●Bartonella serology (ie, IgM and IgG antibodies).
●Bartonella PCR testing, if available.
Because at least 5 percent of the general population has positive IgG titers to Bartonella, a positive test should be interpreted in the context of the patient's epidemiologic and clinical features. Furthermore, antibody production in response to B. quintana infection appears to vary. As an example, patients with acute febrile illness or endocarditis typically develop high-level antibody titers, whereas those with chronic B. quintana bacteremia often have lower-level antibody response [6,7]. Once individuals recover from chronic infection, low-level detectable titers usually persist.
Histopathology does not typically play a role in the diagnosis of B. quintana infections, except in persons with HIV who have cutaneous bacillary angiomatosis or in persons with endocarditis who have undergone valve replacement surgery. If a tissue sample is obtained, we ask the laboratory to perform Bartonella cultures and PCR on the tissue. Bartonella organism can also be identified in a Warthin-Starry tissue stain, but this process is very time consuming and may not be available at some laboratories.
Extensive discussion of the microbiologic diagnosis of bartonella infections is found separately. (See "Microbiologic diagnosis of Bartonella infections".)
Additional evaluation
Evaluate for endocarditis — Patients with a B. quintana febrile illness or bacteremia should undergo careful evaluation for endocarditis, including echocardiography, since endocarditis is treated differently and can have serious complications. Diagnosis and echocardiography of bartonella endocarditis is discussed in detail separately (See "Endocarditis caused by Bartonella".)
Evaluate for underlying predisposing conditions — Patients diagnosed with infections due to B. quintana should undergo thorough evaluation to identify underlying risk factors.
●Physical examination for evidence of lice infestation (eg, pruritus, visualization of live lice or nits) or poor hygiene
●Clinical history for suggestion of substance use disorder (eg, alcohol, injection drug use), housing situation, and risk factors for HIV.
●HIV testing. (See "Screening and diagnostic testing for HIV infection".)
DIFFERENTIAL DIAGNOSIS — The differential diagnosis for B. quintana infections depends on the clinical syndrome.
●Febrile illness – The differential for febrile illnesses is very broad but can be narrowed in patients with recurrent periodic fevers living in crowded conditions where lice infestations can occur. Examples include the following:
•Louse-borne relapsing fever – This syndrome, which primarily occurs in Africa, is acquired from lice and is caused by Borrelia recurrentis. Patients have recurrent fevers with three- to six-day intervals between episodes. The diagnosis is usually made by identifying the organism in thin and thick smears of blood. (See "Microbiology, pathogenesis, and epidemiology of relapsing fever" and "Clinical features, diagnosis, and management of relapsing fever".)
•Tick-borne relapsing fever – This illness is caused by infection with a spirochete (Borrelia species) and the organism is transmitted by the soft tick Ornithodorus. In the United States, this disorder predominantly occurs in western states. The clinical illness and diagnosis are similar to louse-borne relapsing fever.
•Epidemic typhus – This infection is acquired from lice and is caused by Rickettsia prowazekii. It is primarily reported in Africa and the rural highlands of South America and Asia. The diagnosis is made by serologic antibody tests. (See "Epidemic typhus".)
•Tuberculosis – Infection with M. tuberculosis is often associated with prolonged periods of intermittent fevers, usually with cough and abnormal chest imaging. (See "Pulmonary tuberculosis: Clinical manifestations and complications".)
•Malaria – Patients with malaria typically have intermittent daily fevers, but later stage illness is characterized by periodic fevers every one to three days. The diagnosis is made by visualizing the organism on thin and thick blood smears or by positive antigen tests. (See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children".)
•Typhoid and paratyphoid fever (ie, enteric fever) – This infection is caused by specific strains of Salmonella, spreads by fecal-oral route, and occurs primarily in Africa and south Asia in crowded areas with poor sanitation. The diagnosis is made by positive stool or blood cultures. (See "Enteric (typhoid and paratyphoid) fever: Epidemiology, clinical manifestations, and diagnosis".)
•Endocarditis – Individuals who are homeless who inject drugs are at particular risk for bacterial and fungal endocarditis, particularly staphylococcal endocarditis, which may present subacutely. Blood cultures are generally positive if patients have not received prior antibiotic therapy. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis".)
•Endemic fungal infections – Infections, such as histoplasmosis and coccidioidomycosis, can present with recurrent febrile syndromes. Endemic fungal infections are typically diagnosed with serology, antigen testing, or biopsy. (See "Diagnosis and treatment of disseminated histoplasmosis in patients without HIV", section on 'Diagnosis of disseminated histoplasmosis' and "Coccidioidomycosis: Laboratory diagnosis and screening", section on 'Diagnostic tests'.)
•Nontuberculous mycobacterial infections – These infections can cause chronic fever, malaise, and weight loss. In patients with advanced HIV, disseminated M. avium complex is not uncommon, and the diagnosis is made by culturing the organism from blood. (See "Mycobacterium avium complex (MAC) infections in persons with HIV".)
•Malignancy – Many malignancies can cause recurrent fever (eg, lymphoma, renal cell carcinoma, acute lymphoblastic leukemia). The Pel-Ebstein fever associated with Hodgkin's lymphoma is characterized by fevers that cyclically increase then decrease over one to two weeks. (See "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults".)
●Bacillary angiomatosis and bacillary peliosis hepatitis – The differential diagnosis for these syndromes is found separately. (See "Bartonella infections in people with HIV", section on 'Bacillary angiomatosis' and "Bartonella infections in people with HIV", section on 'Bacillary peliosis hepatis and splenitis'.)
TREATMENT — Management of B. quintana infections consists of antibiotic therapy and treatment of underlying predisposing conditions.
Antibiotic selection — Data regarding antibiotic selection for B. quintana infections are scarce; there are no randomized trials directly comparing antibiotic regimens.
Febrile illness or bacteremia — For patients with either of these syndromes in whom endocarditis has been ruled out, we suggest combination therapy with doxycycline and rifampin.
Preferred regimen
●Doxycycline (100 mg orally every 12 hours) for 28 days, PLUS
●Rifampin (300 mg orally every 12 hours) for 14 days.
Doxycycline is the key component of therapy for serious bartonella infections [42]. For patients who cannot take oral therapy, intravenous formulations can be used.
Combination therapy versus monotherapy for treatment of febrile illness or bacteremia without endocarditis has not been evaluated in studies. However, for patients with bartonella endocarditis, retrospective data suggest that combining doxycycline with at least 14 days of gentamicin increases the likelihood of recovery compared with monotherapy with doxycycline [43]. We favor rifampin (despite its lack of clinical data) as the second agent because of gentamicin's increased risk of nephrotoxicity [42]. Both rifampin and gentamicin provide intracellular activity against the organism.
Treatment of asymptomatic patients with B. quintana bacteremia has been found to eradicate infection. In a randomized trial of 20 individuals experiencing homelessness in France who had positive screening blood cultures, treatment with doxycycline and gentamycin was significantly associated with clearance of bacteremia compared with no treatment [44]. Among those who completed the protocol, eradication of B. quintana occurred in all seven treated patients compared with two of nine untreated patients.
Alternative therapy
●Replacement for doxycycline – If doxycycline is not an option, we use combination therapy with azithromycin (500 mg orally or intravenously once daily) for 28 days and rifampin for 14 days, as dosed above.
Clinical data supporting azithromycin are limited, but erythromycin has been used effectively for treatment of bartonella infections in patients with HIV [45,46]; we favor azithromycin due to patients' frequent intolerance of erythromycin.
●Replacement for rifampin – For patients who cannot take rifampin, we combine doxycycline with gentamicin (3 mg/kg/day intravenously once daily, adjusted to achieve trough serum concentrations of <1 mcg/mL, for 14 days).
Gentamicin has been commonly used as a second agent for treatment of serious bartonella infections [42]. Renal function should be monitored for patients taking gentamicin.
Trimethoprim-sulfamethoxazole, fluoroquinolones, penicillins, and first-generation cephalosporins probably do not have reliable activity against B. quintana and are not recommended.
Endocarditis — Patients with endocarditis require a longer duration of antibiotics, closer monitoring, and long-term follow-up. Specific treatment recommendations for bartonella endocarditis are found separately. (See "Endocarditis caused by Bartonella".)
Bacillary angiomatosis and peliosis hepatitis — Treatment of these syndromes is discussed in detail separately. (See "Bartonella infections in people with HIV", section on 'Bacillary angiomatosis' and "Bartonella infections in people with HIV", section on 'Bacillary peliosis hepatis and splenitis'.)
Adjunctive therapies — In addition to treatment with antibiotics, management of predisposing underlying conditions should be addressed, if possible.
Lice infestation is typically treated with topical therapies but sometimes requires oral antimicrobial therapy. Household contacts should be examined for evidence of lice infection, and household cleaning recommendations should be provided. More information regarding management of lice is found separately. (See "Pediculosis capitis", section on 'Treatment' and "Pediculosis corporis", section on 'Management' and "Pediculosis pubis and pediculosis ciliaris", section on 'Management'.)
Other predisposing conditions should be treated as well, including HIV and substance use disorder. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach" and "Alcohol use disorder: Treatment overview" and "Substance use disorders: Psychosocial management".)
Education regarding personal hygiene and social interventions to address housing instability are also helpful, if applicable.
PROGNOSIS — With the exception of endocarditis, death rarely occurs in either the acute or chronic forms of illness [2,36]. During the World War I outbreaks of trench fever, no deaths were reported even though there were no antimicrobial treatments available at that time [42]. Limited data suggest that patients with B. quintana endocarditis have higher attributable mortality rates than other causes of endocarditis; in a retrospective review of 38 patients with confirmed B. quintana endocarditis, three patients (8 percent) died as a consequence of their infection [47].
INFECTION PREVENTION — Treatment of underlying predisposing conditions in infected patients and evaluation of household members helps to prevent recurrences in individual patients, as discussed above. (See 'Adjunctive therapies' above.)
In health care settings, standard precautions suffice for patient management, unless the patient has lice. Providers should follow their hospital policies for management of hospitalized patients with lice; we use contact precautions for our hospitalized patients with lice.
For patients with B. quintana infection and lice who live in congregated living facilities or are homeless, reporting the infection to public health authorities allows identification of outbreak settings.
SUMMARY AND RECOMMENDATIONS
●Geography – B. quintana has a worldwide distribution, although clinically significant infections are uncommon globally. (See 'Geography' above.)
●Vector of transmission – The primary route of spread is via exposure to infected lice. (See 'Transmission' above.)
●Risk factors – Infestation with lice is a major risk factor. As such, crowded household environments with poor hygienic conditions are associated with infection. HIV, alcohol use disorder, and injection drug use may be additional risk factors. (See 'Risk factors' above.)
●Clinical manifestations – Several syndromes can be caused by B. quintana.
•Febrile illness – This form of infection is characterized by fever and malaise that may be self-limited or cause chronic infection. Classic trench fever findings include bone pain in the shins and periodic fevers every four to five days that last four to five days before resolving after several weeks. Other nonspecific fever patterns are more common in contemporary illness. (See 'Febrile illness' above.)
•Chronic bacteremia – After resolution of febrile events, prolonged asymptomatic bacteremia can persist for weeks to months. (See 'Chronic bacteremia' above.)
•Endocarditis – Data suggest that 20 to 43 percent of patients with B. quintana bacteremia have endocarditis. The organism is also a significant cause of culture-negative endocarditis. (See 'Endocarditis' above.)
•Bacillary angiomatosis and bacillary peliosis hepatis – These syndromes occur in patients with advanced HIV (CD4 counts <100 cells/microL). Patients with bacillary angiomatosis present with vascular lesions usually involving the skin. Peliosis hepatis presents with abdominal pain, hepatosplenomegaly, and elevated alkaline phosphatase. (See 'Bacillary angiomatosis' above and 'Bacillary peliosis hepatitis' above.)
●Diagnosis – A definitive diagnosis of Bartonella infection is made by identifying the organism from culture or polymerase chain reaction (PCR) of blood or tissue. However, because culturing Bartonella is difficult, the diagnosis is often made based on positive serologic antibody tests (IgM or IgG) which provide supportive, but not definitive, evidence of infection. (See 'Diagnosis' above.)
●Additional evaluation – Patients with a B. quintana febrile illness or bacteremia should undergo careful evaluation for endocarditis, including echocardiography. (See 'Evaluate for endocarditis' above.)
Physical examination and history should seek evidence of lice, and HIV testing should be performed. (See 'Evaluate for underlying predisposing conditions' above.)
●Antibiotic selection
•Febrile illness or bacteremia – For patients with either of these conditions, we suggest combination therapy with doxycycline (100 mg orally or intravenously every 12 hours) for 28 days, PLUS rifampin (300 mg orally or intravenously every 12 hours) for 14 days (Grade 2C). (See 'Antibiotic selection' above.)
•Endocarditis, bacillary angiomatosis, and bacillary peliosis hepatis – Antibiotic selection for these conditions is discussed in detail separately. (See "Endocarditis caused by Bartonella", section on 'Antimicrobial therapy' and "Endocarditis caused by Bartonella", section on 'Surgery' and "Bartonella infections in people with HIV", section on 'Specific syndromes'.)
●Adjunctive therapy – Lice should be treated with topical or oral agents, as discussed separately. (See "Pediculosis corporis", section on 'Management' and "Pediculosis capitis", section on 'Treatment'.)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
