TYPHUS FEVERS

TYPHUS FEVERS - Jeremy Golding, MD
BASICS
DESCRIPTION
• Acute infectious diseases caused by 3 species of rickettsiae
- Epidemic typhus: Human-to-human transmission by body louse vector. Primarily in circumstances such as refugee camps, war, famine, and disaster. Recrudescent disease (Brill-Zinsser Disease), occurring years after initial infection, can be source of human outbreak. Flying squirrels are also a reservoir.
- Endemic (murine) typhus: Infection by rodents. To humans by rat flea bite.
- Scrub typhus: Infection and infestation of chiggers and of rodents. To humans by the chigger. Primarily in Asia and Western Pacific areas.
• System(s) Affected: Endocrine/Metabolic; Hemic/Lymphatic/Immunologic; Pulmonary; Skin/Exocrine
• Synonym(s): Louse-borne typhus; Brill-Zinsser disease; Murine typhus
GENERAL PREVENTION
Avoid vectors for each disease
• Scrub typhus: Wear protective clothing and use insect repellents.
• Endemic typhus: Practice ectoparasite and rodent control.
• Epidemic typhus: Delousing and cleaning of clothing; vaccine may be considered for those at high risk of exposure (typhus vaccine production has been discontinued in the US).
EPIDEMIOLOGY
• Epidemic and endemic typhus: Rare in US
• Scrub typhus: Travelers returning from endemic areas only (rare)
Incidence
Endemic typhus: 100 cases annually, primarily in states around Gulf of Mexico, especially south Texas, under-reporting suspected
RISK FACTORS
• Exposure to vectors (e.g., during travel to countries where endemic)
• Elderly may have more severe disease
ETIOLOGY
• Epidemic typhus by Rickettsia prowazekii
• Endemic typhus by R. typhi
• Scrub typhus by R. tsutsugamushi


DIAGNOSIS
SIGNS AND SYMPTOMS
• General
- Acute onset
- Fever
- Chills
- Headache
- Myalgia
- Malaise
- Diffuse organ involvement (e.g., intestine, liver, heart, kidneys, brain)
• Epidemic typhus
- Incubation period ~1 week
- Macular or maculopapular rash, begins on trunk spreads to extremities about 5th day of illness
- Nonproductive cough
- Pulmonary infiltrates
- Conjunctivitis
- Neurologic involvement
• Endemic typhus
- Incubation period 1-2 weeks
- Macular or maculopapular rash beginning on trunk 3rd-5th day of illness, spreads to trunk ~5th day
- Duration 12 days untreated
- Usually milder illness
• Scrub typhus
- Incubation period 1-3 weeks
- Eschar at bite site
- Regional lymphadenopathy
- Generalized lymphadenopathy
- Splenomegaly
- Macular or maculopapular rash beginning on trunk about the 5th day of illness
- Relative bradycardia early in disease
- Ocular pain
- Conjunctival injection
History
Travel or other risk exposure
Physical Exam
As above
TESTS
Specific serologic test showing a rising antibody titer. Isolation of Rickettsia should be undertaken only in special laboratories, to minimize risk of laboratory-acquired infection.
Lab
• Leukocyte findings usually normal
• Abnormalities reflecting the particular organs affected
• Weil-Felix serologic reaction may be positive; test value limited to mid-illness or after, and by low sensitivity and specificity. Epidemic and endemic typhus, 4-fold titer rise or titer >1/320 to OX-19. Scrub typhus, 4-fold rise in titer to OX-K.
• Hyponatremia in severe cases
• Hypoalbuminemia in severe cases
• Drugs that may alter lab results: Prior antibiotic use
Pathological Findings
Diffuse vasculitis
DIFFERENTIAL DIAGNOSIS
• Any acute febrile disease
• Rocky Mountain spotted fever
• Meningococcemia
• Bacterial meningitis
• Mediterranean spotted fever (boutonneuse fever) (R. conorii)
• Measles
• Rubella
• Toxoplasmosis
• Leptospirosis
• Typhoid fever
• Dengue
• Relapsing fever
• Secondary syphilis
• Viral syndromes: Mononucleosis, acute retroviral syndrome
TREATMENT
STABILIZATION
Outpatient care unless severely ill
GENERAL MEASURES
• Protect agitated patient from injury
• Skin and mouth care
• Supportive care for the severely ill, directed at the complications
Diet
As tolerated
Activity
Bed rest during acute stages, otherwise as tolerated
MEDICATION (DRUGS)
First Line
• Treatment should begin when diagnosis is reasonably likely and continue until the patient's state is improved and the patient is afebrile for a minimum of 48 hours. Usual treatment course: 5-7 days.
• Children 8 years of age and adults
- Tetracycline, or a congener: 25 mg/kg PO initially, and then 25 mg/kg/d in equally divided doses q6h
- If severely ill, may use doxycycline IV: Adults 100 mg q12h, children 8 years of age 5 mg/kg/d (maximum of 200 mg/d)
• Children 8 years of age, pregnant women, or if typhoid fever is possible cause of illness
- Chloramphenicol: 50 mg/kg PO initially, and then 50 mg/kg daily in equally divided doses q6h
- If severely ill, chloramphenicol sodium succinate: 20 mg/kg IV initially, infused over 30-45 minutes, and then 50 mg/kg/d infused in equally divided doses q6h until orally tolerable
• Precautions: Refer to the manufacturer's profile for each drug.
• Significant possible interactions: Refer to the manufacturer's profile for each drug.
Second Line
• Doxycycline: Single oral dose of 100 or 200 mg for those in refugee camps, victims of disasters, or in presence of limited medical services
• Isolated reports indicate that erythromycin and ciprofloxacin are effective.
FOLLOW-UP
DISPOSITION
Admission Criteria
Severely ill or constitutionally unstable (e.g., shock)
PROGNOSIS
• Recovery is expected if treatment is instituted before onset of complications.
• Relapses may follow treatment, especially if initiated within 48 hours of onset (this is not an indication to delay treatment). Relapses are treated same as primary disease.
• Without treatment, mortality rate of typhus is 40-60% for epidemic, 1-2% for endemic, and up to 30% for scrub. Mortality is higher among the elderly.
COMPLICATIONS
• Consequences of specific organ system involvement in the 2nd week (e.g., azotemia, meningoencephalitis, seizures, delirium, coma, myocardial failure, hyponatremia, hypoalbuminemia, hypovolemia, and shock)
• Death
PATIENT MONITORING
Severely ill patients should be observed regularly in the hospital. Outpatients should be checked periodically as improvement is evident.
REFERENCES
1. Azad AF, Beard CB. Rickettsial pathogens and their arthropod vectors. Emerg Infect Dis. 1998;4:179-186.
2. Azad AF, et al. Flea-borne rickettsioses: Ecologic considerations. Emerg Infect Dis. 1997;3:319-327.
3. Dumlev JS, Taylor JP, Walker DH. Clinical and laboratory features of murine typhus in south Texas, 1980 through 1987. JAMA. 1991;266:1365-1370.
4. Jensenius M, Forunier PE, Raoult D. Rickettsioses and the international traveler. Clin Infect Dis. 2004;39:1493-1499.
5. Mandell GL, Bennett JF, Dolin R, eds. Principles and Practice of Infectious Diseases, 6th ed. New York: Churchill Livingstone, 2004.
6. Raoult D, Roux V. The body louse as a vector of reemerging human diseases. Clin Infect Dis. 1999;29:888-911.
7. Watt G, Parola P. Scrub typhus and tropical rickettsioses. Curr Opin Infect Dis. 2003;16:429-436.
MISCELLANEOUS
• Severe headache is often intractable and not eased by the standard drugs.
• Report case to appropriate health department or other agency.