Rickettsial spotted fevers

Rickettsia
Scientific classification
Kingdom: Bacteria Phylum: Proteobacteria Class: Alpha Proteobacteria Order: Rickettsiales Family: Rickettsiaceae Genus: Rickettsia da Rocha-Lima, 1916
Species
Rickettsia felis Rickettsia prowazekii Rickettsia rickettsii Rickettsia typhi Rickettsia conorii Rickettsia africae etc.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.; Kiran Singh, M.D. [2]

Overview

Rickettsia is a genus of non-motile, Gram-negative, non-sporeforming, highly pleomorphic bacteria that can present as cocci (0.1 μm in diameter), rods (1-4 μm long) or thread-like (10 μm long). Obligate intracellular parasites, the Rickettsia depend on entry, growth, and replication within the cytoplasm of eukaryotic host cells (typically endothelial cells). Because of this, Rickettsia cannot live in artificial nutrient environments and are grown either in tissue or embryo cultures (typically, chicken embryos are used). In the past they were regarded as microorganisms positioned somewhere between viruses and true bacteria. The majority of Rickettsia bacteria are susceptible to antibiotics of the tetracycline group.

Rickettsia species are carried as parasites by many ticks, fleas, and lice, and cause diseases such as typhus, rickettsialpox, Boutonneuse fever, African Tick Bite Fever, Rocky Mountain spotted fever, Australian Tick Typhus, Flinders Island Spotted Fever and Queensland Tick Typhus in human beings. They have also been associated with a range of plant diseases. Like viruses, they grow only in living cells. The name rickettsia is often used for any member of the Rickettsiales. They are thought to be the closest living relatives to bacteria that were the origin of the mitochondria organelle that exist in most eukaryotic cells.

The method of growing rickettsia in chicken embryos was invented by Ernest William Goodpasture and colleagues at Vanderbilt University in the early 1930s.

Howard Taylor Ricketts (1871-1910) an American Pathologist credited with the discovery of the Rickettsiacae family of bacteria which causes Rocky Mountain Spotted Fever. He was also credited with the discovery of the tick vector, the Rocky Mountain Wood tick.

Etymology

• The genus Rickettsia is named after Howard Taylor Ricketts (1871–1910), who worked on and eventually died of typhus.

Human pathogenesis

• Transmission occurs as a result of a bite from an infected tick or mite as well as the fecal content of rickettsia infected fleas and lice.
• Rickettsiae enter the bloodstream following inoculation.
• Infection usually occurs within the endothelium as well as smooth muscle cells.
• Bacterial infection progresses with binary fission within the cytosol.
• Infected target cells undergo immense damage.
• A host defense includes a T-lymphocyte-mediated immunological response.
• This includes the presence of gamma interferons and tumor necrosis factor alpha.

Genomics

• Certain segments of Rickettsial genomes resemble that of mitochondria.
• The deciphered genome of R. prowazekii is 1,111,523 bp long and contains 834 protein-coding genes.
• Unlike free-living bacteria, it contains no genes for anaerobic glycolysis or genes involved in the biosynthesis and regulation of amino acids and nucleosides.
• In this regard it is similar to mitochondrial genomes; in both cases, nuclear (host) resources are used. ATP production in Rickettsia is the same as that in mitochondria.
• In fact, of all the microbes known, the Rickettsia is probably the closest "relative" (in phylogenetic sense) to the mitochondria.
• The genome of R. prowazekii contains a complete set of genes encoding for the tricarboxylic acid cycle and the respiratory-chain complex.
• The genomes of the Rickettsia as well as the mitochondria are frequently said to be "small, highly derived products of several types of reductive evolution".

Classification of rickettsial diseases

Disease	Organism	Vector	Endemic Regions
Rocky Mountain Spotted Fever	Rickettsia Rickettsii	Wood Tick (Dermacentor Variabilis), D. andersoni	United States: Eastern Region Southwest Region
Helvetica Spotted Fever	Rickettsia Helvetica	Ixodes Ricinus (European)	Europe: Sweden Switzerland France Laos
Ehrlichiosis Anaplasmosis	Ehrlichia Chaffeensis, E. Equi	Lone Star Tick (Amblyomma Americanum), Ixodes Scapularis	United States: South Atlantic Regions South-central Regions
Tularemia	Francisella Tularensis	D. Andersoni, D. Variabilis	United States: Widespread throughout the region, including higher populations in the Southeast, South-central, and the West.
Human neoehrlichiosis	Neoehrlichia mikurensis	Lone Star Tick (Amblyomma Americanum)'	Widespread: Europe Asia
Rickettsiosis	Rickettsia	No specific species identified	Widespread: South Africa Morocco Mediterranean
African tick-bite fever	Rickettsia africae	Amblyomma, Dermacentor, and Rhipicephalus species	Africa: Sub-Saharan West Indies
Queensland tick typhus	Rickettsia austalis	Ixodes species	Widespread: Australia Tasmania
Q-fever (Typhus-like infection)	Coxiella burnetii (mimics the mechanisms of Rickettsia)	Ixodes holocyclus and Amblyomma triguttatum	Australia Widespread throughout Australia
Mediterranean spotted fever (Boutonneuse fever)	Rickettsia conorii	Brown Dog Tick (Rhipicephalus sanguineus)	Widespread: Southern Europe Southern and Western Asia Africa India
Far Eastern spotted fever	Rickettsia heilong-jiangensis	Tick	Widespread: Far portions of Eastern Russia Northern portions of China Eastern Asia
Aneruptive fever	Rickettsia helvetica	Ixodes species	Widespread: Northern and Central portions of Europe Non-specific portions of Asia
Flinders Island spotted fever (Thai tick typhus)	Rickettsia honei	Tick	Widespread in Independent Regions Australia Thailand
Japanese spotted fever	Rickettsia japonica	Tick	Japan Widespread yet isolated to portions of Japan
Mediterranean spotted fever-like disease	Rickettsia massiliae and R. monacensis	Tick	Widespread: R.massiliae induced: France Greece Spain Portugal Switzerland Sicily Central Africa Mali R.monacensis induced: Europe North Africa
Maculatum infection	Rickettsia parkeri	Tick	Americas: United States Portions of Canada South America
Tick-borne necrosis and lymphadenopathy	Rickettsia raoultii	Dermacentor marginatus	Widespread: Europe Asia
North Asian Tick Typhus	Rickettsia sibirica	Tick	Widespread: Russia China Mongolia
Lymphangitis	Rickettsia sibirica mogolotimonae	'No specific species identified	Widespread: Southern France Portugal China Africa
TIBOLA	Rickettsia slovaca	Dermacentor species	Widespread: Southern and Eastern Europe Asia

Differentiating between common rickettsial diseases

Disease	Symptoms
Typhus (Rickettsia)
Rocky Mountain Spotted Fever	Fever, alterations in mental state, myalgia, rash, and headaches.
Helvetica Spotted Fever	Rash: spotted, red dots. Respiratory symptoms (dyspnea, cough), muscle pain, and headaches.
Ehrlichiosis Anaplasmosis	Fever, headache, chills, malaise, muscle pain, nausea, confusion, conjunctivitis, or rash (60% in children and 30% in adults).
Tularemia	Ulceroglandular, Glandular, Oculoglandular, Oroglandular, Pneumonic, Typhoidal.

Diagnosis

Physical examination

• Characterized by flu-like symptoms and blistering rashes.
• If the disease is caused by an infected tick, an eschar, or cutaneous necrosis, is visible at the site of inoculation.

Laboratory diagnostics

• A confirmatory diagnosis requires a comparative analysis of an acute-phase and convalescent-phase serum antibody titers.

Risk Factors

• Traveling or residing within endemic regions will increase chances of infection.
• Tick activity is generally heightened during certain the spring and summer months.
• Within endemic regions, tick may choose an animal host, including a domesticated animal such as a dog or cat.
• Although rare, cases of blood transfusion and organ transplantation have been recorded as methods of transmission.
• All together, individuals who spend time outdoors and/or have pets that go outdoors in endemic regions are at risk for tick-borne disease.

Treatment

Medical Therapy

• Antibiotic treatment is often justified based on clinical presentation alone. However all clinical treatments must be tailored according to a patients personal profile; considering age, immunocompetance, pregnancy, allergen profile, splenic function, and current medical status.
• If there is a collection of pus, the area will need to be incised and drained.

Disease	Treatment
Typhus (Rickettsia)
Rocky Mountain Spotted Fever	Antibiotics Doxycycline Tetracycline
Helvetica Spotted Fever	Antibiotics Broad-spectrum antibiotic therapy Penicillin
Ehrlichiosis Anaplasmosis	Antibiotics Doxycycline, dosages should begin prior to lab results if ehrlichiosis is suspected. Adults: 100 mg PO q12h for 7-14 days Children (under 100lbs/45kg): 2.2 mg/kg PO q12h for 7-14 days
Tularemia	Antibiotics Streptomycin Gentamicin Doxycycline Ciprofloxacin
Other Spotted Fevers (Rickettsia bacterial infections)	Antibiotics Doxycycline Adults: 100 mg PO q12h for 7-14 days Children (under 100lbs/45kg): 2.2 mg/kg PO q12h for 7-14 days

Prevention

• Rickettsia infections are most often caused by the bite of an infected mite or tick.
• Tick transmission occurs over the course of a blood meal, therefore the early and proper removal of an infected tick may help evade a potential infection. (For instructions on properly removing a tick, please see "the best way to remove a tick" section below.
• Avoidance of endemic areas is the most effective tactic in preventing a rickettsial infection.
• If it's impossible to avoid endemic areas, common techniques to limit tick exposure may be found in the "limiting tick exposure" section below.
• Other methods of transmission include the fecal matter of infected lice and mites. Thus prevention would include maintaining proper hygiene.

Limiting tick exposure

Tuck pants into socks

It is unreasonable to assume that a person can completely eliminate activities that may result in tick exposure. Therefore, prevention measures should emphasize personal protection when exposed to natural areas where ticks are present:

• Wear light-colored clothing which allows you to see ticks that are crawling on your clothing.
• Tuck your pants legs into your socks so that ticks cannot crawl up the inside of your pants legs.
• Apply repellents to discourage tick attachment. Repellents containing permethrin can be sprayed on boots and clothing, and will last for several days. Repellents containing DEET (n, n-diethyl-m-toluamide) can be applied to the skin, but will last only a few hours before reapplication is necessary. Use DEET with caution on children. Application of large amounts of DEET on children has been associated with adverse reactions.
• Conduct a body check upon return from potentially tick-infested areas by searching your entire body for ticks. Use a hand-held or full-length mirror to view all parts of your body. Remove any tick you find on your body.
• Parents should check their children for ticks, especially in the hair, when returning from potentially tick-infested areas.
• Ticks may also be carried into the household on clothing and pets and only attach later, so both should be examined carefully to exclude ticks.

The best way to remove a tick

1. Use fine-tipped tweezers or notched tick extractor, and protect your fingers with a tissue, paper towel, or latex gloves. Persons should avoid removing ticks with bare hands.
2. Grasp the tick as close to the skin surface as possible and pull upward with steady, even pressure. Do not twist or jerk the tick; this may cause the mouth-parts to break off and remain in the skin. (If this happens, remove mouth-parts with tweezers. Consult your health care provider if illness occurs.)
3. After removing the tick, thoroughly disinfect the bite site and wash your hands with soap and water.

Tick removal process

• Do not squeeze, crush, or puncture the body of the tick because its fluids may contain infectious organisms. Skin accidentally exposed to tick fluids can be disinfected with iodine scrub, rubbing alcohol, or water containing detergents.

Removal of an embedded tick using fine-tipped tweezers

• Save the tick for identification in case you become ill. This may help your doctor to make an accurate diagnosis. Place the tick in a sealable plastic bag and put it in your freezer. Write the date of the bite on a piece of paper with a pencil and place it in the bag.

Future or investigational therapies

• The recent discovery of another parallel between Rickettsia and viruses may become a basis for fighting HIV infection.
• Human immune response to the scrub typhus pathogen, Orientia tsutsugamushi rickettsia, appears to provide a beneficial effect against HIV infection progress, negatively influencing the virus replication process.
• A probable reason for this actively studied phenomenon is a certain degree of homology between rickettsia and the virus - namely, common epitope(s) due to common genome fragment(s) in both pathogens.
• Another infection reported to be likely to provide the same effect (decrease in viral load) is the virus-caused illness dengue fever.

External links

• Rickettsia (from PATRIC the PathoSystems Resource Integration Center, a NIAID Bioinformatics Resource Center)

• African Tick Bite Fever [3] from Centre for Disease Control and Prevention [4]

Related Chapters

• Rocky Mountain Spotted Fever
• Ehrlichiosis
• Relapsing fever
• Tick-borne disease