The disease presentation can range from mild viral-like illness to moderate and finally into a debilitating disease process. Patients who present with cases of trench fever are assumed to likely be bacteremic. The hallmark of this disease process is fever. Fever can present in multiple ways. These include an isolated febrile episode, febrile episodes lasting four to five days, three to five recurrent febrile episodes lasting five days with asymptomatic periods in between, and persistent febrile episodes for two to six weeks.[6][7] Other presenting symptoms include malaise, fever, headache, dizziness, bone pain (particularly of the shins), nausea, vomiting, and weight loss.

Physical examination on documented cases typically has febrile episodes with temperatures generally greater than 38.4 degrees Celsius (101.1 Fahrenheit). Some patients have palpable splenomegaly, and also a maculopapular rash is noted mainly in the truncal area.[7]

Bartonella quintana is difficult to culture. There are recommendations to culture on ethylenediaminetetraacetic acid (EDTA) bottles or chocolate agar under 5% carbon dioxide incubated at 35 degrees Celsius. It is a slow-growing fastidious bacterium, and so cultures should be held for at least 21 days.[8] Because of its slow growth, there are cases documented of utilizing polymerase chain reaction. (PCR) According to Zeaiter et al., species-specific reverse-transcriptase polymerase chain reaction (RT PCR) was compared to serology, which helped diagnose all three Bartonella species. Finally, trench fever may be diagnosed by serology, but this has been recorded to be most sensitive in cases with endocarditis.[9]

Optimal management for trench fever is uncertain due to limited published data. The recommended treatment depends on the patient's presentation. For acute or chronic infection, doxycycline 200mg for four weeks daily in combination with gentamicin 3 mg/kg intravenously once daily for the first 14 days. If gentamicin is not an option due to availability, allergies, or other contraindications, rifampin 300 mg twice a day for the first 14 days is recommended. The treatment was thoroughly detailed in the randomized, open-label trial, conducted by Foucault et al., where complete eradication was noted per-protocol analysis in seven out of seven patients treated with combination therapy in comparison to two out of nine patients who received no treatment with P = 0.003.[10][11] Gentamicin levels, especially in patients with renal impairment, should be monitored closely. Finally, patients with chronic trench fever should be evaluated with echocardiogram for endocarditis, as this would lead to a prolonged course of antibiotics.

Malaria

The Plasmodium parasite transmitted by the female Anopheles mosquito leads to characteristic cyclical fevers. There are five species known as Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax, Plasmodium malariae, and Plasmodium knowlesi. Symptoms may be similar to trench fever, such as headache, malaise, weakness, gastrointestinal distress, and muscle aches. However, there may be distinguishing traits in severe cases, including jaundice, confusion, seizures, and dark urine. If this diagnosis is recognized, the gold standard for diagnosis is a microscopic evaluation of Giemsa-stained thick and thin smears of a blood sample.[12]

Typhus

This is caused by Salmonella typhi and Salmonella paratyphi. Symptoms consist of nausea and vomiting, which may progress to diffuse abdominal pain, bloating, anorexia, and diarrhea with or without blood. This disease may also result in bacteremia. If typhoid fever is suspected, blood cultures should be obtained.

Relapsing Fever

Patients typically present with symptoms of recurrent fevers, chills, and malaise. This is caused by a spirochete known as Borrelia recurrentis, and diagnosis may be made via Giemsa-stained blood films, serologic analysis, or PCR.

Leptospirosis

The anicteric presentation can have similar symptoms to trench fever, such as headache, cough, non-pruritic rash, fever, rigors, muscle pain, anorexia, and diarrhea. The icteric presentation, also known as Weil's disease, may present with renal failure, jaundice, hemorrhage, and respiratory distress. This disease should be considered and diagnosed by specialized culture or microscopic agglutination test (only available at the CDC in Atlanta).[13] 

Rocky Mountain Spotted Fever (RMSF)

Initial symptoms include fever, headaches, and rash, which is typically petechial but can also be maculopapular. The differentiating feature from trench fever is the rash’s progression, which is usually extremities to the trunk. Other symptoms can include lymphadenopathy, and central nervous system changes, mainly confusions or nuchal rigidity, myalgias and arthralgias, hepatitis, gastrointestinal distress, and cardiovascular instability. RMSF is diagnosed by immunoglobulin M (IgM) and immunoglobulin G (IgG) serology.

There is limited documentation on the prognosis of trench fever. Some patients do not require treatment as the infection may result in a self-limited illness. However, due to increasing documentation of bacteremia, recommendation to treat the disease takes precedence. Prognosis can also differ based on the patient's immune status. More severe cases leading to critical complications and worse prognosis are observed in patients with human immunodeficiency viruses (HIV), transplantation on immunosuppressants, and alcoholism.

There are cases reported of Bartonella quintana causing endocarditis from chronically infected patients and bacillary angiomatosis, mainly in immunocompromised patients. Patients documented to present with endocarditis typically have chest pain, shortness of breath, weight loss, night sweats, and other non-specific symptoms of malaise, cough, and fatigue. The examination usually mimics the classic endocarditis. This includes new cardiac murmurs, Janeway lesions, Osler nodes, and vascular and immunologic phenomena.[14][15] 

Organisms most common for blood culture-negative endocarditis include but are not limited to Bartonella, Coxiella, Chlamydia, Legionella, Mycoplasma, Aspergillus, and Brucella.[15] It is very crucial to evaluate for these pathogens. In France, according to Fournier et al., Bartonella is the causative organism in approximately 20% of all charted cases of blood culture-negative endocarditis.[16]

Bacillary angiomatosis is very common in patients with cell-mediated immunodeficiency such as HIV and posttransplant patients on immunosuppressive therapy. Bartonella quintana can induce new blood vessel formation, which leads to angioproliferative tumors.[17] This occurs after a high concentration of the organism has accumulated in an immunocompromised host. According to Chiraviglio et al., Bartonella organisms express surface adhesins and stick easily to one another.[18]

It is essential to discuss the adverse effects of medication, such as doxycycline with patients. This includes photosensitivity with teaching on avoidance of prolonged sun exposure and also wearing protective garments. It is important to maintain sanitary environments to prevent transmission.

Trench fever can present as non-specific symptoms but should be considered in patients known to live in clustered areas with inadequate hygiene. It is essential to find all Bartonella species, including B. quintana, in blood culture-negative endocarditis to avoid further treatment delay. Consider utilizing polymerase chain reaction in addition to blood culture for diagnosis. Consider adding an aminoglycoside, especially in severely ill patients with endocarditis who are at risk for Bartonella quintana infection.

Because trench fever may result in a spectrum of disease ranging from mild, non-specific symptoms to severe debilitating illness, it can help consult a specialist early in the course of illness. These patients are best managed with an interprofessional team approach. It is important to consult an infectious disease specialist and a cardiologist if a patient is diagnosed with endocarditis or bacillary angiomatosis.