Murine Typhus- Symptoms and Treatment

Introduction

Murine typhus is a rare disease caused by an infection from rickettsia typhi bacteria that spreads through parasitic contact. The condition is zoonotic involving fleas or lice; rats, dogs, or cats, and humans. Rats, mice, cats, opossums, and dogs often act as reservoirs for bacteria. The disease does not spread from person to person but rather requires vectors.

Who Is Susceptible to Murine Typhus?

The disease is endemic in temperate and coastal regions, especially in the United States, Asia, Australia, México, and Spain. The condition is also found in different species of wild mammals spread throughout the globe like rodents, opossums, dogs, and as well as imported by travelers and refugees. The incidence of Murine typhus has shown seasonal variation, with a higher incidence in warm weather and lower in cool weather when the infection rate tends to zero. The condition is prevalent in all age groups but relatively common in children. There is no significant gender, racial, or occupational predilection. People living in rural or disadvantaged areas are highly prone to infection.

What Causes Murine Typhus?

The etiological agent of murine typhus belongs to the Tifus group of the Rickettsiaceae Family from the Rickettsiales order of organisms. The specific organism Rickettsia typhi and Rickettsia prowazekii are causative agents of murine typhus. Both organisms are genetically similar with a difference in cell surface protein (omp-A and omp-B) and lipopolysaccharides. Both bacteria are located in the cellular cytoplasm at the time of infection and get freed when Rickettsia enters the cell by inducing phagocytosis.

What Is the Transmission Cycle of Murine Typhus Infection?

The Rickettsia typhi (causative bacteria) life cycle is composed of mammal hosts (animals and humans) and a vector (fleas). The natural cycle of this agent includes two rat species and opossums as reservoirs and the flea species (ctenocephalides felis and xenophilia cheopis) as a vector. The bacteria enters the flea from the rats and the flea carries the infection throughout its life without dying off of it. Humans get infected in three different ways: self-inoculated from feces of fleas in the bite area and nails, bite and inhalation of flea-infected feces, and involvement of reservoir animals and vectors.

1. Urban Cycle: The rat species xenophilia cheopis acts as the host for the plea. The pathogen enters the circulatory system of the rat and subsequently enters back into the flea during its blood meals. The rat flea does not exclusively feed on rat blood, it seeks other reservoirs in the absence of a rat. The urban cycle is a common route of transmission in overcrowded cities with unsanitary conditions.

2. Suburban Cycle: In the suburban cycle, feral, domestic cats, and peridomestic opossums act as reservoirs of the bacteria. Domestic cats are the most prone to be infected by flea bites. The cats and opossums interact in the suburban neighborhood entering backyards in search of food, water, and nesting sites.

The incubation period varies between seven to 14 days after exposure following which the symptoms appear.

3. Pathogeny: Rickettsial pathogeny depends on an intracytoplasmic niche rich in nutrients and meets its growth requirements inside the host cell. The cell is essential for intracellular replication and diffusion. The organism enters the lymphatic and blood through the respiratory or cutaneous paths and reaches its main target-the endothelial cells. The endothelial injury is an important medium in the pathogenic and pathophysiology of endemic typhus.

The bacteria adhere to endothelial cells with the outer membrane proteins -omp-B. Immediately after the adhesion, the bacteria penetrate the endothelial cells by phagocytosis. The invasion requires the presence of certain cholesterol-rich microdomains and the ubiquitin ligase. The bacteria are capable of escaping quickly into the cytoplasm before the fusion phase lysosome through a phospholipase activity. The infection infiltrates nearby cells by a peculiar mechanism affecting the rearrangement of actin and endothelial cell production with the involvement of free oxygen radicals.

What Are the Signs and Symptoms of Murine Typhus?

The symptoms of flea-borne typhus appear within two weeks after inoculation from an unnoticed infected flea bite or flea dirt.

The signs and symptoms are:

• High fever.

• Chills.

• Body aches.

• Muscle pain.

• Loss of appetite.

• Nausea.

• Vomiting.

• Confusion.

• Diarrhea.

• Stupor.

• Hypotension.

• Photosensitivity.

• Stomach pain.

• Cough.

• Rash.

• Swollen lymph nodes.

The progression to severe forms is rare and most patients recover without any treatment. Untreated illness can increase the severity and damage to one or multiple organs including the liver, kidneys, heart, lungs, and brain.

Severe symptoms include:

• Splenic rupture.

• Endocarditis (infection of the heart lining).

• Meningitis (infection of the meninges-covering of the neurons).

• Aseptic meningitis (non-bacterial inflammation of the meninges).

• CNS complications.

• Serious neurological signs.

• Brain and spinal cord inflammation.

• Enlarged spleen.

• Inflammation of the heart muscle or valves.

• Internal bleeding.

• Septic shock.

How to Diagnose Murine Typhus?

The diagnosis is based on the clinical manifestations recognized by a primary physician who then orders several investigations that gives a confirmatory report of typhus infection. The physician also takes into account the living conditions of the individual, the presence of typhus outbreaks in the community, and the history of international travel.

Blood Tests:

• Anemia (lack of hemoglobin in the blood).

• Decreased or elevated WBC (white blood cell) count.

• Elevated ESR (erythrocyte sedimentation rate) count.

• Thrombocytopenia (low platelet count).

• Elevated aminotransferase levels.

• Hypoalbuminemia (low blood albumin levels).

Serological testing require a comparison of acute to convalescent phase serology and can be used to identify the genus of the bacteria.

A skin biopsy from a sample of the skin from the rash is to be tested in the lab. Western blotting can be used to determine the presence of typhus. The immunofluorescence test uses fluorescent dyes to detect typhus antigens in serum taken from the bloodstream.

How to Treat Murine Typhus?

The most preferred treatment regimen against typhus is antibiotic therapy with Doxycycline. Chloramphenicol is indicative of infection but is contraindicated in pregnant and nursing mothers. Ciprofloxacin is prescribed to adults with Doxycycline allergy.

The regimen also includes preventive measures by breaking the cycle and vector control:

• Keeping rodents and animals away from residential, commercial, and recreational areas.

• Removal of bushes, rocks, junk, cluttered firewood, and food supplies, especially pet food around habitation.

• Use an EPA-approved (environmental protection agency-approved) insect repellant during outdoor activities.

• Treating clothes and accessories with permethrin or purchasing permethrin-treated items.

• Keeping pets flea-free and regularly examining pets for such infestations.

• Applying an effective insect repellent, like DEET (N, N diethyl-3-methyl benzamide).

• Washing clothes and bed linen regularly.

What Is the Prognosis of Murine Typhus?

All variants of rickettsial typhus bacterial infection can prove fatal, yet murine typhus tends to be much less severe. Early treatment is very effective with almost 100 % remissions and relapses are uncommon after completing the full antibiotic course. Delayed treatment and misdiagnosis can increase the severity. Older individuals are at higher risk of mortality. Murine typhus, without treatment, is fatal in less than four percent of the cases.

What Is the Differential Diagnosis of Murine Typhus?

• Dengue fever.

• Typhoid.

• Rickettsial spotted fevers.

• Scrub typhus.

• Melioidosis.

• Viral illness.

What Are the Complications of Murine Typhus?

• Hepatitis.

• Gastrointestinal hemorrhage.

• Hypovolemia.

• Renal insufficiency.

• Pneumonia.

• Central nervous system damage.

Conclusion

Murine typhus is an infectious condition but the spread can be limited by breaking the cycle. The prevention means include self-care, surrounding areas, and pet care. Early recognition and treatment with prevention can dissuade typhus from taking an endemic spread. The lack of availability of vaccines has not shown a difference in the outcome of the condition.