EM@3AM: Murine Typhus
- Dec 1st, 2024
- Grant Gerstner
- categories:
Authors: Grant Gerstner, DO (EM Resident Physician, San Antonio, TX); Kyle Smiley, MD (EM Resident Physician, San Antonio, TX) // Reviewed by: Sophia Görgens, MD (EM Physician, BIDMC, MA); Cassandra Mackey, MD (Assistant Professor of Emergency Medicine, UMass Chan Medical School); Alex Koyfman, MD (@EMHighAK)
Welcome to EM@3AM, an emDOCs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.
A 52-year-old male with a history of essential hypertension presents to your South Texas ED for his second visit this week complaining of indolent fever, shortness of breath, pleuritic chest pain, and a rash on his trunk and extremities. He was diagnosed with a viral syndrome three days ago but his symptoms have worsened despite supportive treatments. Upon further questioning, he reports adopting a stray cat one week ago.
Vital signs include BP 96/82, HR 115, T 102.1, RR 36, and SpO2 89% on RA. On exam, he appears uncomfortable. He is tachycardic and tachypneic with diffuse crackles and rhonchi. His skin exam is notable for a diffuse maculopapular rash covering his trunk and proximal extremities. His chest x-ray is pictured below.
What is the diagnosis?
Answer: Murine Typhus
Epidemiology:
- Murine typhus is endemic in several parts of the U.S.:
- Southern Texas
- Over 5,800 cases of flea-borne typhus were reported between 2008 and 2022 [max = 738 cases/year (2018); min = 135 cases/year (2010)]1
- Southern California
- 744 total cases of flea-borne typhus with estimated symptom onset dates from 2013 through 20192
- Hawaii
- 5-6 cases annually, with large outbreak of 47 cases in 20023
- Southern Texas
- Worldwide, most cases occur in subtropical regions with cases reported on 6 continents4
- Mortality between 1-4% if untreated5
Pathophysiology:
- Caused by bacteria Rickettsia typhi and Rickettsia felis6,7
- Gram negative coccobacillus, intracellular pathogens
- Incubation period of 1-2 weeks
- Vector: Rat Fleas (Xenopsylla cheopis), Cat Fleas (Ctenocephalides felis)
- Reservoirs: Murine mammals, rodents, opossums, cats, and dogs
- Incidental Host: Humans
Clinical Presentation:
- History of exposure to mammalian reservoirs, most often strays or flea-infested animals
- Subjective findings are nonspecific8,9
- Fevers, chills, headache, shortness of breath, cough, arthralgias, nausea, vomiting, and diarrhea
- Objective findings are also nonspecific
- Vitals: Febrile, hypoxia, tachypnea, tachycardia, hypotension
- Physical Exam: Altered mental status, papular/maculopapular rash, excoriations, bug bites, coarse breath sounds, hepatomegaly, abdominal tenderness
Evaluation:
- Labs
- Infectious/septic workup8,9
- CBC, CMP, VBG, Lactate, Procalcitonin
- Leukocytosis, transaminitis, lactic acidosis, elevated procalcitonin
- Blood cultures are often negative, as R. typhi is an intracellular pathogen10
- Obtain cultures to rule out other infectious causes
- PCRs, skin biopsies and immunoassays can be used but are not available in all facilities
- Rickettsia spp IFA and/or NAAT are often not available but can be sent with high index of suspicion11
- CBC, CMP, VBG, Lactate, Procalcitonin
- Infectious/septic workup8,9
- Imaging
- Chest X-ray9
- May see focal consolidation, pulmonary effusion, pulmonary edema
- POCUS has utility, particularly in septic shock (RUSH exam)
- Can assess volume status and may see pulmonary edema in severe cases12
- Chest X-ray9
Treatment:
- ABCs
- Resuscitate if hemodynamically unstable with airway management, IV fluids, and vasopressors
- Up to 28% experience severe complications (bronchiolitis, pneumonia, meningitis, septic shock, cholecystitis, pancreatitis, myositis, and rhabdomyolysis)9, 13
- Antimicrobial Therapy
- Doxycycline: first line for otherwise healthy, nonpregnant adults
- 100 mg BID for 7 to 14 days or until 3 days of defervescence
- Likely safe in children and pregnancy, especially in severe illness where risk of morbidity and mortality is high14,15,16
- Due to difficulty obtaining definitive diagnosis, in sick patients with high index of suspicion, treat empirically as benefits likely outweigh risks according to FDA15
- Second line: Chloramphenicol, azithromycin, or fluoroquinolones17
- Doxycycline: first line for otherwise healthy, nonpregnant adults
- Decontamination if patient has fleas present
- Remove and dispose of patient’s clothing/linens
- Contact environmental services for fumigation as required per institutional policy
Disposition:
- If stable, patient may be discharged with atypical antimicrobial coverage, with doxycycline as the preferred first line agent
- If unstable, focus on the resuscitation and admit for IV antibiotics
- While not a reportable communicable disease, consider a consultation to Infectious Disease for alternative diagnoses, local antibiotic susceptibility, and available diagnostic testing
Pearls:
- Murine typhus is endemic in the United States to Southern Texas, Southern California, and Hawaii, although, some cases have occurred outside of these regions
- Suspect murine typhus if patient has potential exposure to flea bites (think rats, opossums, stray cats, and dogs)
- Suspect R. typhi infection if treatment is refractory to supportive measures or conventional community-acquired pneumonia antibiotics
- Treat with atypical bacterial coverage (doxycycline, azithromycin, chloramphenicol, or fluoroquinolones)
A 32-year-old woman presents to the ED with a fever and rash after returning from a trip to Southeast Asia. She reports fever, headache, malaise, and a maculopapular rash that started on her trunk and has spread to her extremities, as shown above. She reports seeing numerous rats in the area where she was staying. Her vital signs are a T of 102.3°F (39.1°C), BP of 110/70 mm Hg, HR of 100 bpm, RR of 18/min, and SpO2 of 98% on room air. Her blood tests show the following:
Hemoglobin: 14 g/dL
WBC: 6,000/µL
Platelets: 120,000/µL
Sodium: 130 mEq/L
Albumin: 3.0 g/dL
Creatine kinase: 190 U/L
Aspartate aminotransferase: 50 U/L
Alanine aminotransferase: 55 U/L
What is the best initial treatment for this patient?
A) Azithromycin
B) Chloramphenicol
C) Ciprofloxacin
D) Doxycycline
E) Trimethoprim-sulfamethoxazole
Answer: D
This patient presents with fever, headache, malaise, and a maculopapular rash after returning from an area in Southeast Asia where she reports seeing numerous rats. This raises suspicion for murine typhus, a rickettsial disease caused by Rickettsia typhi, transmitted by fleas that infest rats. The laboratory findings, including mild thrombocytopenia, hyponatremia, and mildly elevated liver enzymes, are consistent with murine typhus.
While primarily transmitted by fleas from rats, other animals like cats and opossums may be involved. The disease occurs worldwide, with hotspots in areas where rats accumulate in large numbers, such as Southeast Asia, North Africa, and the Mediterranean. In the US, cases are sporadically reported, mostly in states like Texas, California, and Hawaii. Murine typhus is often underdiagnosed due to its nonspecific symptoms, which can easily be mistaken for a viral illness, and because many patients are unaware of flea exposure.
The clinical presentation of murine typhus includes fever, headache, myalgias, and occasionally gastrointestinal symptoms like nausea, vomiting, and diarrhea. A maculopapular rash develops in about half of patients, typically starting on the trunk and spreading peripherally. Severe complications are rare but can include kidney dysfunction, respiratory distress, and neurologic symptoms like meningitis or encephalitis. The disease is generally mild, but in untreated cases, it can lead to more severe outcomes, especially in patients with underlying conditions such as glucose-6-phosphate dehydrogenase deficiency.
Diagnosis of murine typhus relies on clinical suspicion, particularly in travelers or individuals with potential flea exposure who present with fever and rash. Laboratory findings are nonspecific, but common abnormalities include thrombocytopenia, hyponatremia, elevated liver function tests, and sometimes mild cerebrospinal fluid abnormalities. Definitive diagnosis is often made using serologic testing, typically by detecting a fourfold rise in antibody titers between acute and convalescent samples. PCRtests are also available but not widely used due to sensitivity issues.
The treatment for murine typhus typically involves doxycycline, which is considered the first-line therapy for adults and children. The usual duration of doxycycline treatment is 7–10 days or at least 48 hours after the patient becomes afebrile. In pregnant patients, azithromycin is often preferred due to concerns about doxycycline’s potential effects on fetal development. However, some experts recommend doxycycline even in pregnant patients. Treatment significantly shortens the duration of illness, and early initiation of therapy can prevent severe complications and reduce the length of hospitalization. Even though the disease often resolves spontaneously, prompt antibiotic therapy is essential for optimal outcomes.
Azithromycin (A) can be used in some rickettsial infections for patients who cannot tolerate doxycycline (e.g., pregnant patients). However, doxycycline is the preferred first-line treatment for murine typhus.
Chloramphenicol (B) is not commonly used due to the risk of serious side effects, including bone marrow suppression. It is reserved for severe cases or in settings in which doxycycline is unavailable.
Ciprofloxacin (C) is not effective for rickettsial diseases and is typically used for bacterial infections such as urinary tract infections or gastrointestinal infections.
Trimethoprim-sulfamethoxazole (E) is ineffective against rickettsial infections and may worsen the condition in cases of rickettsial diseases.
