Question

short detailed summary on, the Rocky mountain spotted fever.

name of the microbial disease

causative agent

signs and symptoms

pathologenesis and virulence factors

transmission & epidemiology

prevention & treatment

Answer 1

Rocky Mountain spotted fever (RMSF) is a bacterial disease spread by ticks. It typically begins with a fever and headache, which is followed a few days later with the development of a rash. The rash is generally made up of small spots of bleeding and starts on the wrists and ankles. Other symptoms may include muscle pains and vomiting. Long-term complications following recovery may include hearing loss or loss of part of an arm or leg.

Name of microbial disease-

Blue disease, Brazilian spotted fever, Tobia fever, new world spotted fever, tick- borne typhus fever, Sao Paulo fever

Causative agent- Rickettsia rickettsii

Symptoms

Spotted fever can be very difficult to diagnose in its early stages, due to the similarity of symptoms with many different diseases.

People infected with R. rickettsii usually notice symptoms following an incubation period of one to two weeks after a tick bite. The early clinical presentation of Rocky Mountain spotted fever is nonspecific and may resemble a variety of other infectious and noninfectious diseases.

Initial symptoms:

• Fever
• Nausea
• Emesis (vomiting)
• Severe headache
• Muscle pain
• Lack of appetite
• Parotitis in some cases (somewhat rare)

Later signs and symptoms:

• Maculopapular rash
• Petechial rash
• Abdominal pain
• Joint pain
• Conjunctivitis
• Forgetfulness

The classic triad of findings for this disease are fever, rash, and history of tick bite. However, this combination is often not identified when patients initially present for care. The rash has a centripetal, or "inward" pattern of spread, meaning it begins at the extremities and courses towards the trunk.

RashEdit

The rash first appears two to five days after the onset of fever, and it is often quite subtle. Younger patients usually develop the rash earlier than older patients. Most often the rash begins as small, flat, pink, nonitchy spots (macules) on the wrists, forearms, and ankles. These spots turn pale when pressure is applied and eventually become raised on the skin. The characteristic red, spotted (petechial) rash of Rocky Mountain spotted fever is usually not seen until the sixth day or later after onset of symptoms, but this type of rash occurs in only 35 to 60% of patients with Rocky Mountain spotted fever. The rash involves the palms or soles in as many as 80% of people. However, this distribution may not occur until later on in the course of the disease. As many as 15% of patients may never develop a rash.

Pathogenesis

Entry into host

Rickettsia rickettsii can be transmitted to human hosts through the bite of an infected tick. As with other bacterium transmitted via ticks, the process generally requires a period of attachment of 4 to 6 hours. However, in some cases a Rickettsia rickettsii infection has been contracted by contact with tick tissues or fluids.^[15] Then, the bacteria induce their internalization into host cells via a receptor-mediated invasion mechanism.

Researchers believe that this mechanism is similar to that of Rickettsia conorii. This species of Rickettsia uses an abundant cell surface protein called OmpB to attach to a host cell membrane protein called Ku70. It has previously been reported that Ku70 migrates to the host cell surface in the presence of "Rickettsia".Then, Ku70 is ubiquitinated by c-Cbl, an E3 ubiquitin ligase. This triggers a cascade of signal transduction events resulting in the recruitment of Arp2/3 complex. CDC42, protein tyrosine kinase, phosphoinositide 3-kinase, and Src-family kinases then activate Arp2/3. This causes the alteration of local host cytoskeletal actin at the entry site as part of a zipper mechanism.^[17] Then, the bacteria is phagocytosized by the host cell and enveloped by a phagosome.^[16]

Studies have suggested that rOmpB is involved in this process of adhesion and invasion. Both rOmpA and rOmpB are members of a family of surface cell antigens (Sca) which are autotransporter proteins; they act as ligands for the Omp proteins and are found throughout the rickettsiae.

Exit from host cell

The cytosol of the host cell contains nutrients, adenosine triphosphate, amino acids, and nucleotides which are used by the bacteria for growth. For this reason, as well as to avoid phagolysosomal fusion and death, rickettsiae must escape from the phagosome. To escape from the phagosome, the bacteria secrete phospholipase D and hemolysin C. This causes disruption of the phagosomal membrane and allows the bacteria to escape. Following generation time in the cytoplasm of the host cells, the bacteria utilizes actin based motility to move through the cytosol.

RickA, expressed on the rickettsial surface, activates Arp2/3 and causes actin polymerization. The rickettsiae use the actin to propel themselves throughout the cytosol to the surface of the host cell. This causes the host cell membrane to protrude outward and invaginate the membrane of an adjacent cell.

The bacteria are then taken up by the neighboring cell in a double membrane vacuole that the bacteria can subsequently lyse, enabling spread from cell to cell without exposure to the extracellular environment.

Consequences of infection

Rickettsia rickettsii initially infect blood vessel endothelial cells, but eventually migrate to vital organs such as the brain, skin, and the heart via the blood stream. Bacterial replication in host cells causes endothelial cell proliferation and inflammation, resulting in mononuclear cell infiltration into blood vessels and subsequent red blood cell leakage into surrounding tissues. The characteristic rash observed in Rocky Mountain spotted fever is the direct result of this localized replication of rickettsia in blood vessel endothelial cells.

Virulence factor

During bacterial endothelial infection, R. rickettsii first gets into endothelial cells using surface adhesion proteins, OmpA and OmpB, which help them quickly attach to and pass into endothelial cells, a process called endocytosis

These surface protein attract macrophages to eat bacteria. After engulf Bacteria use secretion system T4ASS to secrete toxin to kill macrophage and escape by being eaten.

Transmission

Rickettsiae are transmitted to humans by the bite of infected ticks and mites and by the feces of infected lice and fleas. They enter via the skin and spread through the bloodstream to infect vascular endothelium in the skin, brain, lungs, heart, kidneys, liver, gastrointestinal tract, and other organs

Epidemiology

All travelers are at risk of acquiring rickettsial infections during travel to endemic areas. Transmission occurs throughout the year but is increased during outdoor activities. Because of the 5- to 14-day incubation period for most rickettsial diseases, tourists may not experience symptoms during their trip, and onset may coincide with their return home or within a week after returning. Although the most commonly diagnosed rickettsial diseases in travelers are usually in the spotted fever or typhus groups, travelers may acquire a wide range of rickettsioses, including emerging and newly recognized species not well known by many health care providers

There are between 500 and 2500 cases of Rocky Mountain spotted fever reported in the United States per year,and in only about 20% can the tick be found.

Host factors associated with severe or fatal Rocky Mountain spotted fever include advanced age, male sex, African or Caribbean background, chronic alcohol abuse, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Deficiency of G6PD is a genetic condition affecting about 12 percent of the Afro-American male population. Deficiency in this enzyme is associated with a high proportion of severe cases of Rocky Mountain spotted fever.This is a rare clinical complication that is often fatal within five days of the onset of the disease.

In the early 1940s, outbreaks were described in the Mexican states of Sinaloa, Sonora, Durango, and Coahuila driven by dogs and Rhipicephalus sanguineus sensu lato, the brown dog tick.Over the ensuing 100 years case fatality rates were 30%–80%. In 2015, there was an abrupt rise in Sonora cases with 80 fatal cases. From 2003 to 2016, cases increased to 1394 with 247 deaths.

Prevention

Prevention of rickettsial infections

• Exclusion of people with rickettsial infections from childcare, preschool, school and work is not necessary.
• There is no vaccine available to prevent infection.
• Wear long sleeved protective clothing and a broad brimmed hat to reduce the risk of infection when undertaking activities where human contact with ticks, lice, mites or fleas may occur, such as bushwalking and camping in infected areas.
• Use an insect repellent containing DEET or picaridin and examine your skin for possible bites (especially behind the ears, on the back of the head, in the groin, armpits and behind the knees) following these activities

Treatment

Appropriate antibiotic treatment should be started immediately when there is a suspicion of Rocky Mountain spotted fever. Early treatment of Rocky Mountain spotted fever prevents further damage to internal organs. Treatment should not be delayed for laboratory confirmation. Failure to respond to a tetracycline argues against a diagnosis of Rocky Mountain spotted fever. Severely ill people may require longer periods before their fever resolves, especially if they have experienced damage to multiple organ systems. Preventive therapy in healthy people who have had recent tick bites is not recommended and may only delay the onset of disease.

Doxycycline (a tetracycline) is the drug of choice for patients with Rocky Mountain spotted fever, being one of the only instances doxycycline is used in children.Treatment typically consists of 100 milligrams every 12 hours, or for children under 45 kg (99 lb) at 4 mg/kg of body weight per day in two divided doses. Treatment should be continued for at least three days after the fever subsides, and until there is unequivocal evidence of clinical improvement. This will be generally for a minimum time of five to ten days.Severe or complicated outbreaks may require longer treatment courses. Doxycycline/ tetracycline is also the preferred drug for patients with ehrlichiosis, another tick-transmitted infection with signs and symptoms that may resemble those of Rocky Mountain spotted fever. Chloramphenicol is an alternative drug that can be used to treat Rocky Mountain spotted fever, specifically in pregnancy. However, this drug may be associated with a wide range of side effects, and careful monitoring of blood levels is required.