BASICSDouglas W. MacPherson, MD, MSc—CTM, FRCPC
BASICS
Typhus is an infectious disease syndrome caused by several rickettsial bacterial organisms resulting in acute, chronic, and recurrent disease (1)[C].
DESCRIPTION
• Acute infection caused by three species of Rickettsia
– Epidemic typhus: human-to-human transmission by body louse; primarily in setting of refugee camps, war, famine, and disaster. Recurrent disease occurs years after initial infection and can be a source of human outbreak. Flying squirrels are a reservoir.
– Endemic (murine) typhus: spread 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; hematologic/lymphatic/immunologic; pulmonary; skin/exocrine
• Synonym(s): louse-borne typhus; Brill-Zinsser disease; murine typhus
EPIDEMIOLOGY
• Epidemic and endemic typhus: rare in the United States (outside of South Texas)
• Scrub typhus: travelers returning from endemic areas only (rare)
Incidence
Endemic typhus: <100 cases annually, primarily in states around the Gulf of Mexico, especially South Texas; underreporting suspected
ETIOLOGY AND PATHOPHYSIOLOGY
• Epidemic typhus by Rickettsia prowazekii
• Endemic typhus by Rickettsia typhi
• Scrub typhus by Rickettsia tsutsugamushi
RISK FACTORS
• Vector exposure
• Travel to endemic countries
Geriatric Considerations
Elderly may have more severe disease.
GENERAL PREVENTION
Vector control:
• Scrub typhus: Wear protective clothing and use insect repellents.
• Endemic typhus: Practice ectoparasite and rodent control.
• Epidemic typhus: delousing and cleaning of clothing; vaccine for those at high risk of exposure (typhus vaccine production has been discontinued in the United States)
DIAGNOSIS
Typhus syndromes are rare in the United States. A high level of clinical suspicion is necessary.
HISTORY
Travel or other risk exposure
• Fever, chills
• Intractable headache
• Myalgias, malaise
• Cough, rash, ocular pain
PHYSICAL EXAM
• General
– Fever
– Relative bradycardia (scrub typhus)
• Epidemic typhus
– Incubation period ~1 week
– Macular or maculopapular rash beginning on trunk ~5th day of illness
– Nonproductive cough
– Pulmonary infiltrates
• Endemic typhus
– Incubation period 1 to 2 weeks
– Macular or maculopapular rash beginning on trunk 3rd to 5th day of illness
• Scrub typhus
– Incubation period 1 to 3 weeks
– Eschar at bite site
– Regional lymphadenopathy
– Generalized lymphadenopathy
– Splenomegaly
– Macular or maculopapular rash beginning on trunk approximately 5th day of illness
– Relative bradycardia early in disease
– Ocular pain
– Conjunctival injection
DIFFERENTIAL DIAGNOSIS
• Other rickettsial disease: Rocky Mountain spotted fever; ehrlichiosis; Mediterranean spotted fever (boutonneuse fever) (Rickettsia conorii)
• Bacterial meningitis; meningococcemia
• Measles, rubella
• Toxoplasmosis
• Leptospirosis
• Typhoid fever
• Dengue, malaria
• Relapsing fever
• Secondary syphilis
• Viral syndromes: mononucleosis, acute retroviral syndrome
DIAGNOSTIC TESTS & INTERPRETATION
• Specific serologies with rising antibody titer
• If suspected, isolate Rickettsia in qualified laboratory to minimize the risk of laboratory-acquired infection.
• CDC Rickettsial Zoonoses Branch 404-639-1075.
Initial Tests (lab, imaging)
• CBC often normal
• Weil-Felix serologic reaction may be positive; test value hampered by low sensitivity and nonspecificity; 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
• Recent antibiotic exposure may alter lab results.
Test Interpretation
Diffuse vasculitis on skin biopsy
TREATMENT
Initiate treatment based on epidemiologic risk and clinical presentation.
GENERAL MEASURES
• Skin and mouth care
• Supportive care for the severely ill, directed at complications
First Line
• Begin treatment when diagnosis is likely and continue until clinically improved and the patient is afebrile for at least 48 hours; usual course is 5 to 7 days.
• Children ≥8 years of age and adults
– Doxycycline IV/PO: adults 100 mg q12h, children ≤45 kg: 5 mg/kg/day divided twice daily (max of 200 mg/day); >45 kg: adult dosing
– Children ≤8 years of age: Risk of dental staining from tetracyclines is minimal with short courses of therapy.
– Tetracycline: 25 mg/kg PO initially, then 25 mg/kg/day in equally divided doses q6h
• Children ≤8 years of age, pregnant women, or if typhoid fever is suspected
– Chloramphenicol: 50 mg/kg PO initially, then 50 mg/kg/day in equally divided doses q6h
– If severely ill, chloramphenicol sodium succinate: 20 mg/kg IV initially, infused over 30 to 45 minutes, then 50 mg/kg/day infused in equally divided doses q6h until orally tolerable
– Azithromycin, fluoroquinolones, and rifampin may be alternatives depending on the clinical scenario.
• 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 orally for those in refugee camps, victims of disasters, or in the presence of limited medical services
• Isolated reports indicate that erythromycin and ciprofloxacin are effective.
• Azithromycin 1,000 mg orally once a day for 3-day course is effective for scrub typhus; better tolerated than doxycycline but more expensive
• Rifampin may be effective in areas where scrub typhus responds poorly to standard antirickettsial drugs.
ISSUES FOR REFERRAL
Infectious disease consultation is recommended. Contact CDC and local public health authorities.
ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS
• Outpatient care unless severely ill
• Severely ill or constitutionally unstable (e.g., shock)
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
• Admit severely ill patients.
• If treated as an outpatient, ensure regular follow-up to assess clinical improvement and resolution.
DIET
As tolerated
PATIENT EDUCATION
Travel advice (minimize exposure risks, vector avoidance, vaccination as appropriate)
PROGNOSIS
• Recovery is expected with prompt treatment.
• Relapses may follow treatment, especially if initiated within 48 hours of onset (this is not an indication to delay treatment). Treat relapses the same as primary disease.
• Without treatment, the mortality rate of typhus is 40–60% for epidemic, 1–2% for endemic, and up to 30% for scrub disease.
• Mortality is higher among the elderly.
COMPLICATIONS
Organ-specific complications (particularly in the second week of illness): azotemia, meningoencephalitis, seizures, delirium, coma, myocardial failure, hyponatremia, hypoalbuminemia, hypovolemia, shock, and death
REFERENCES
1. Centers for Disease Control and Prevention. McQuiston J. Rickettsial (spotted and typhus fevers) and related infections (anaplasmosis and ehrlichiosis). http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/rickettsial-spotted-typhus-fevers-related-infections-anaplasmosis-ehrlichiosis. Accessed 2015.
ADDITIONAL READING
• Botelho-Nevers E, Raoult D. Host, pathogen and treatment-related prognostic factors in rickettsioses. Eur J Clin Microbiol Infect Dis. 2011;30(10):1139–1150.
• Botelho-Nevers E, Rovery C, Richet H, et al. Analysis of risk factors for malignant Mediterranean spotted fever indicates that fluoroquinolone treatment has a deleterious effect. J Antimicrob Chemother. 2011;66(8):1821–1830.
• Botelho-Nevers E, Socolovschi C, Raoult D, et al. Treatment of Rickettsia spp. infections: a review. Expert Rev Anti Infect Ther. 2012;10(12):1425–1437.
• Chikeka I, Dumler JS. Neglected bacterial zoonoses. Clin Microbiol Infect. 2015;21(5):404–415.
• Graham J, Stockley K, Goldman RD. Tick-borne illnesses: a CME update. Pediatr Emerg Care. 2011;27(2):141–147.
• Green JS, Singh J, Cheung M, et al. A cluster of pediatric endemic typhus cases in Orange County, California. Pediatr Infect Dis J. 2011;30(2):163–165.
• Hendershot EF, Sexton DJ. Scrub typhus and rickettsial diseases in international travelers: a review. Curr Infect Dis Rep. 2009;11(1):66–72.
• Molina N. Borders, laborers, and racialized medicalization Mexican immigration and US public health practices in the 20th century. Am J Public Health. 2011;101(6):1024–1031.
• Panpanich R, Garner P. Antibiotics for treating scrub typhus. Cochrane Database Syst Rev. 2002;(3):CD002150.
CODES
ICD10
• A75.9 Typhus fever, unspecified
• A75.0 Epidemic louse-borne typhus fever d/t Rickettsia prowazekii
• A75.2 Typhus fever due to Rickettsia typhi
CLINICAL PEARLS
• Consider typhus (along with malaria and dengue) in febrile travelers returning from endemic areas.
• Rickettsial infections typically present within 2 to 14 days. Febrile illnesses presenting with onset >18 days after travel are unlikely to be rickettsial.
• Routine blood cultures do not detect Rickettsia.
• Prior vaccination does not exclude the diagnosis of typhus.