Patient Presentation
A 20-year-old male was admitted with fever up to 102.6F for 2 days, headache that was worsening and rash that was new on the day of admission. He complained of neck stiffness, nausea without emesis and general malaise as well. The past medical history was non-contributory but the social history was significant for returning from traveling one week ago in several Asian-Pacific countries for the past 8 weeks, including tropical and out of the way areas. He had tried to follow appropriate travel prevention strategies including drinking presumably clean water and using insect repellent consistently. He did remember being bitten by mosquitos and possibly other insects.
The pertinent physical exam had normal vital signs. He appeared ill but had normal mentation. His mucous membranes were slightly tacky and his capillary refill was 2-3 seconds. HEENT showed mild photophobia with neck stiffness. His skin had a flat 2-3 mm diffuse rash that was blanching on the trunk and extremities with possible a few on the palms. There was no obvious eschar. Abdominal examination showed some mild general tenderness with palpation but no hepatosplenomegaly, masses, guarding or point tenderness. He complained of some general muscle aches with palpation. The diagnosis of of possible meningitis was made in the emergency room and the patient underwent a lumbar puncture and other appropriate workup, and was started on intravenous antibiotics and fluids. The admitting team was concerned about travel-based causes of meningitis and consulted an infectious disease specialist who felt that the patient should also be given acyclovir and doxycycline in addition to cover for potential herpes simplex and also various rickettsial diseases. The specialist noted that given the location and the travel history almost anything was a possibility including water-borne diseases, mosquito and other arthropod infections, sexually-transmitted infections, etc. “He could even have some type of typhus with his history,” he remarked. The initial laboratory evaluation showed the lumbar puncture to be most consistent with a viral meningitis and eventually viral studies identified an echovirus. The patient was clinically well enough 5 days later to be discharged and all bacterial testing was negative.
Discussion
Rickettsioses are “small, obligate intracellular, gram-negative, aerobic coccobacillary α-proeobacteria” from the genuses Rickettsia, Anaplasma, Coxiella, Ehrlichia, and Orientia genuses. Often they cause limited health problems but can cause severe disease and death. They present with a fever and other non-specific signs and symptoms, usually with a rash and lymphadenopathy. Other problems can include:
- Cardiac – endocarditis, myocarditis, pericarditis
- Gastrointestinal – abdominal pain, acute abdomen, cholecystitis, hepatitis, pancreatitis
- Heme/Lymph – hemophagocytosis, lymphangitis
- Ocular – papilledema, retinitis, uveitis
- Pulmonary problems including pneumonitis, Acute Respiratory Distress Syndrome
- Renal – acute kidney injury
Laboratory testing can be very non-specific especially early in the disease process and points towards viral diseases (e.g. mild anemia, leucopenia, thrombocytosis, mildly elevated acute phase reactants and transaminases). Diagnosis can be made with indirect immunofluorescence antibody assays made after 7-15+ days of illnesses. Weil-Felix test is basically no longer used. Doxycycline is the drug of choice for most patients of any age including the pediatric age group.
Rickettsial disease are one of the more common causes of fever without a source or fever of unknown origin. The differential diagnosis for rickettsioses includes:
- Drug allergy
- Infectious mononucleosis**
- Kawasaki disease**
- Meningitis – meningococcal meningitis
- Other less common infections – brucellosis, leishmaniasis, leptospirosis
- Sepsis
- Typhoid fever
** – often a primary consideration in US
In the US and Europe, tick-borne rickettsioses are the most common vector.
More common rickettioses in the US and Europe include:
| Disease | Organism | Location | Clinical Findings |
|---|---|---|---|
| Anaplasmosis | Anaplasma phagocytophilus, spread by tick | Western hemisphere: Northeastern and Upper Midwest, and Pacific Coast of US | Fever, rash rarely present, headache, nausea/emesis |
| Babesiosis | Babesia microti, spread by ticks | Western hemisphere: Northeastern and Upper Midwest US | Fever, headache, hepatosplenomegaly, malaise |
| Ehrlichiosis | Ehrlichia chaffeenis, spread by ticks | Western hemisphere: Southeast, Southcentral, Pacific US | Fever, rash less common, headache, nausea/emesis |
| Lyme Disease | Borerelia burgdorferi, spread by ticks | Western hemisphere: Northeastern and Upper Midwest, and Pacific Coast of US | Fever, rash (usually single spreading target-like), lymphadenopathy, headache, myalgia, arthralgia early localized stage. With early disseminated or late may have additional skin lesions, and central nervous system problems, and arthritis |
| Mediterranean Spotted Fever | Rickettsia coroii and others, spread by ticks | Europe and North Africa, sporadic cases in more developed countries | Fever, and rash (often petechiae and/or purpuric) predominate |
| Rocky Mountain Spotted Fever | Rickettsia rickettsii, spread by ticks | Western hemisphere: Eastern US, Mountain West and Southern Deserts US, Mexico and Central America | Fever, rash (often petechael), headache, nausea/emesis |
| Tularemia | Francisella tularenia, spread by ticks | Western hemisphere: Eastern, Mountain West, Southeastern and Southcentral US | Fever, rash (can have eschar), lymphadenopathy, vomiting/diarrhea, malaise |
| Epidemic Typhus (e.g. Typhus fever) | Rickettsia powazekii, spread by body louse | World-wide, Sporadic cases in more developed countries | Fever, rash without eschar (may or may not have rash), lymphadenopathy, vomiting/diarrhea, malaise |
| Endemic or Murine Typhus | Rickettsia typhi or Rickettsia felis by fleas | World-wide, Sporadic cases in more developed countries | Fever, rash (with or with no eschar), headache |
| Scrub Typhus | Orientia tsutsugamushi, spready by mites/chiggers | Asia Pacific, Sporadic cases in more developed countries | Fever, rash (frequently with eschar), lymphadenopathy, headache, myalgia abdominal pain, vomiting, malaise. Causes many deaths where it is common. |
Typhoid fever should not be confused with Typhus fever (e.g. Epidemic Typhus). Typhoid fever is caused by Salmonella typhi or Salmonella paratyphi and causes fever, abdominal pain, headache, nausea, diarrhea. It is spread through contaminated food and water. Vaccine (both oral and injectable) are available for prevention.
Learning Point
Rickettsial diseases should be considered when a patient is unwell with:
- Fever, lymphadenopathy and rash are present in any combination
- Laboratory tests are normal (usually)
- Living or traveled an endemic area
- Had an arthropod bite (but can occur through exposure to feces or infected soil exposure)
- Exposed to social situations where exposure to lice, fleas, and ticks are likely
- Other similar cases in an area
Rickettsial infections occur in urban and rural environments. Also they are not only warm weather infections as they can occur during cold months because of crowded conditions.
Questions for Further Discussion
1. How can you prevent tick bites?
2. How do you interpret cerebral spinal fluid results? A review can be found here
3. What rickettsial diseases are most common in your location?
Related Cases
- Disease: Meningitis | Bacterial Infections | Viral Infections | Bites and Stings
- Symptom/Presentation: Fever and Fever of Unknown Origin | Headaches | Erythematous Maculopapular Lesions
- Specialty: Infectious Diseases | Travel Medicine
- Age: Young Adult
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for these topics: Meningitis, Viral Infections, Bacterial Infections and Insect Bites and Stings.
To view current news articles on this topic check Google News.
To view images related to this topic check Google Images.
To view videos related to this topic check YouTube Videos.
Mukkada S, Buckingham SC. Recognition of and Prompt Treatment for Tick-Borne Infections in Children. Infect Dis Clin North Am. 2015;29(3):539-555. doi:10.1016/j.idc.2015.05.002
Portillo A, Santibanez S, Garcaa-Alvarez L, Palomar AM, Oteo JA. Rickettsioses in Europe. Microbes Infect. 2015;17(11-12):834-838. doi:10.1016/j.micinf.2015.09.009
Galanakis E, Bitsori M. When to Think of Rickettsia. Pediatr Infect Dis J. 2019;38(6S Suppl 1):S20-S23. doi:10.1097/INF.0000000000002320
Sood AK, Sachdeva A. Rickettsioses in Children – A Review. Indian J Pediatr. 2020;87(11):930-936. doi:10.1007/s12098-020-03216-z
Warrell CE, Osborne J, Nabarro L, et al. Imported rickettsial infections to the United Kingdom, 2015-2020. J Infect. 2023;86(5):446-452. doi:10.1016/j.jinf.2023.03.015
Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa