RICKETTSIA RICKETTSII: CHARACTERISTICS, CONTAGION, TREATMENT - BIOLOGY - 2025

Rickettsia rickettsii is a bacterium of the Alphaproteobacteria class of the heterogeneous genus Rickettsia, which is an ancestral group that originated the mitochondria. All riches are pathogenic, with R. rickettsii the most virulent among them.

R. rickettsii is a strict intracellular parasite of eukaryotic cells. Its natural hosts, reservoirs and vectors are the ixodoid mites, commonly known as hard ticks. The latter are hematophagous ectoparasites, that is, they feed on blood.

Figure 1. Rickettsia rickettsii (stained red) within the cytoplasm of a host cell. Source: By CDC, via Wikimedia Commons

Vectors of R. rickettsii are ticks: Dermacentor variabilis, D. andersoni, Rhipicephalus sanguineus and Amblyomma cajennense.

Ricketsia do not survive long outside their host, being transmitted by the arthropod to their progeny (transovarially), and from animal to animal by different routes.

The tick obtains the richesia when it takes blood from an infected animal. Once inside the tick, the richesia penetrate the epithelial cells of its gastrointestinal tract and multiply there. They are then defecated with the insect's feces.

Figure 2. Rickettsia rickettsii vector tick. Source: CDC / Dr. Christopher Paddock acquired from Public Health Image Library (Website). freestockphotos.biz

The tick infects other animals with the richetsia, through its oral apparatus (since while they suck the blood, they also inoculate their infected saliva), or through the feces that it deposits on the skin. The human being participates in the cycle of richesia as an accidental host.

characteristics

R. rickettsii is an infectious agent for many mammals and is pathogenic for humans, in which it causes Rocky Mountain fever (FMR), Rocky Mountain spotted fever (FMMR), or “Q fever”.

This disease is acquired through the bite of an infected tick and therefore has a seasonal presentation associated with the appearance of its vectors or conditioned by ecological changes. The increase in temperature due to global climate change is one of the factors that favors the generalized distribution of the disease vector.

FMR is currently considered a disease with worldwide distribution, although it was previously considered endemic to forested areas of the United States, Central and South America.

Morphology

R. rickettsii is a bacilliary-shaped proteobacterium without flagellum, small (0.3 to 0.5 µm x 1 to 2 µm) and Gram negative (although with characteristic Giemsa staining).

It has a double inner membrane of peptide-glycans and a double outer membrane, as well as a cell wall with muramic and diaminopimelic acid.

It contains a small genome (1 - 1.5 Mpb) and is divided by binary fission, with generation times of 8 hours.

Receptor-mediated mechanism of invasion

Richesia enter the host cell through an active process that has been extensively studied in R. conorii.

Ricketsia are believed to use self-transporting membrane proteins (OmpB, OmpA, peptide B, Adr1, or Adr2), to bind to another host cell membrane protein, which is a DNA-dependent protein kinase (Ku70). The latter only appears in the membrane of the host cell, when found in the presence of richesia.

Finally, the actin of the host cell cytoskeleton is altered, and richetsia-induced phagocytosis occurs when engulfed by a phagosome.

Within the cytoplasm of the host cell

Once in the cytoplasm, the richesia avoids death by phagolysosomal fusion, escaping from the phagosome.

R. rickettsii lives freely and multiplies in the cytoplasm or cell nucleus, where it has access to the host cell's nutrients. Thus it also protects itself from the host's immune response.

Metabolism

R. rickettsii is deficient in many metabolic functions, making it an obligate intracellular parasite. It takes most of the molecules necessary (amino acids, nucleotides, ATP) for its growth and multiplication, from the cell it parasitizes.

It also has a very distinctive energy metabolism, since it is not capable of oxidizing glucose or organic acids like other bacteria, being able only to oxidize glutamic acid or glutamine.

Spread in the host

R. rickettsii moves between neighboring cells inducing actin polymerization of the host cell cytoskeleton. It thus generates invagination of the membrane and passes to the neighboring cell avoiding its exposure to the host's immune system. It can also blow up the host cell.

The spread within the host's body and to all its organs, occurs initially through its lymphatic vessels and then through the blood vessels. It infects a wide variety of host cells in vertebrates: endothelial cells, epithelial cells, fibroblasts, and macrophages. In invertebrates, it infects epithelial cells.

It has the ability to infect insects (ticks), reptiles, birds, and mammals.

Culture

Possible biological weapon

Rickettsia rickettsii is classified as a possible biological weapon according to the document "Public health response to biological and chemical weapons: guide of the World Health Organization (WHO)".

It is considered a highly dangerous microorganism, due to its biological characteristics, such as: its low infectious dose, being a cause of high mortality and morbidity, environmental stability, small size and transmission in aerosol form (infection can occur through the mucosa, either conjunctival or respiratory route).

Biosafety Level 3

According to the United States Center for Disease Control and Prevention, R. rickettsii is a Biosafety Level 3 pathogen. This implies that its dangerousness requires certain precautions during handling, such as:

• The laboratory where it is grown must have particular design and safety features (such as clinical diagnostic laboratories, some research).
• Laboratory personnel must know and apply the protocols for handling pathogens and lethal agents.
• The approved standard operating procedure (SOP) must be followed.
• There must be supervision by experts in their handling and in biosecurity.
• The manipulation of the strains must be carried out within biological safety spaces.

Cultivation methodologies

Richesia cannot be grown on solid or liquid agar. Its cultivation requires cell lines (free of antibiotics) from reptile, bird and mammalian hosts.

Among the cell lines used for its cultivation are: lines derived from human or other mammalian fibroblasts, epithelial and endothelial cells, chicken embryo and tick fibroblasts, among others.

Its traditional cultivation involves the use of embryos of chickens (eggs) or animals susceptible to infection by rickets such as ticks. Other more complex forms of culture involve the use of human and animal blood and tissues.

Few laboratories carry out their identification and isolation, due to the complexity and danger of their culture.

Symptoms of contagion

The incubation period for FMR in humans is 10 to 14 days after the bite of an infected tick (from a pet or from the environment). This disease has the following symptoms:

• The fundamental disease is a vasculitis, or lesions in the endothelium of the blood vessels, which increase capillary permeability.
• Edema at the level of the affected tissues. If it occurs in the lungs or brain, it can be fatal.
• Possible bleeding.
• Kidney and systemic damage in general.
• Typical scab and rash lesion with blackened skin, at the site of the tick bite.
• Sudden high or moderate fever lasting two to three weeks.
• Shaking chills.
• Rash (rash or red patches on the skin), beginning on the arms or legs. They can also be found on the soles of the feet or the palms of the hands, later spreading to the rest of the body.
• Intense headache.
• Severe muscle aches
• Fatigue.
• Pain in the abdomen and joints.
• Nausea, vomiting, and loss of appetite.
• Other nonspecific general manifestations.

Figure 3. Rash or red spots on the skin due to infection with Rickettsia rickettsii. Source: See page for author, via Wikimedia Commons

Mortality

Before the development of antibiotics, FMR produced a mortality rate of up to 80% in some regions. Currently the mortality rate due to this disease ranges from 10 to 30%.

There is currently no available licensed richetsial vaccine.

Treatment

FMR can be controlled if it is diagnosed early and if it is treated with broad spectrum antibiotics such as: Tetracyclines (Doxycycline) and Chloramphenicol (although it generates side effects).

In the following table, taken from Quintero et al. (2012), the recommended antibiotic doses are shown according to the age group and the physiological state of the patient.

Prophylaxis

Vector control

Controlling tick populations in forests is extremely difficult, making FMR eradication almost impossible.

Avoid exposure

To avoid tick bites in infested habitats, it is recommended to wear light-colored clothing, tuck the shirt inside the pants, and overlap the socks on the edge of the pants or the latter inside the boots. Finally, it is recommended to check the skin at the end of the possible exposure to ticks.

Insect repellants can only be useful if applied correctly and in the right doses, since they can be toxic.

If a tick occurs on the skin, the risk of becoming infested with R. rickettsii is minimal if the vector can be removed correctly within 4 hours of attachment.

In case of removing ticks from pets, gloves should be used.

Tick ​​removal

When detecting a tick in the body, it must be carefully removed, avoiding regurgitation, since if infected, it would infect its host. If possible, it is recommended that a physician perform this procedure.

The only recommended way to remove them involves the use of tweezers with narrow and curved tips.

The tick must be held by its mouth area (attached to the host's skin), avoiding crushing its body. Then a slow but continuous traction should be made until it is removed from the skin.

If any remainder of your oral appliance remains inside the skin, it must be removed with a scalpel or needle. After the tick has been removed, the bitten area and hands should be disinfected.

References

1. Abdad, MY, Abou Abdallah, R., Fournier, P.-E., Stenos, J., & Vasoo, S. (2018). A Concise Review of the Epidemiology and Diagnostics of Rickettsioses: Rickettsia and Orientia spp. Journal of Clinical Microbiology, 56 (8). doi: 10.1128 / jcm.01728-17
2. Ammerman, NC, Beier-Sexton, M., & Azad, AF (2008). Laboratory maintenance of Rickettsia rickettsii. Current protocols in microbiology, Chapter 3, Unit 3A.5.
3. McDade, JE, & Newhouse, VF (1986). Natural History of Rickettsia Rickettsii. Annual Review of Microbiology, 40 (1): 287–309. doi: 10.1146 / annurev.mi.40.100186.001443
4. Prescott, LM (2002). Microbiology. Fifth edition. McGraw-Hill Science / Engineering / Math. pp 1147.
5. Quintero V., JC, Hidalgo, M. and Rodas G., JD (2012). Riquettsiosis, an emerging and re-emerging lethal disease in Colombia. Universitas Scientiarum. 17 (1): 82-99.
6. Walker, DH Rickettsiae. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 38.