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Rickettsia rickettsii presentation
- 1. Don’t get Spots when you hike in the Mountains BY: MELISSA VAUGHN RICKETTSIA RICKETTSIA ROCKY MOUNTAIN SPOTTED FEVER
- 2. Case Study In early September, an 8 year old female from Tennessee, presented at the emergency room with a fever over 102 for at least two days. She complained of abdominal pain, nausea, diarrhea, and vomiting. The patient was sent home after a diagnosis of viral gastroenteritis. After two days when the patient didn’t get better her parents took her back to the emergency room with fever (unbroken), anorexia, irritability, cough, abdominal pain mimicking appendicitis, conjunctival injection, nausea, diarrhea and vomiting. Physical examination showed a petechial rash on the trunk, arms, legs, palms, and soles as well as hepatosplenomegaly.
- 3. Case Study Continued… Laboratory results included a WBC count of 11.4 x 109 cells/L; showing increase WBC’s. Thrombocytopenia (72 x 109 platelets/L), elevated aspartate aminotransferase (AST) of 179 U/L (Normal <43 U/L), elevated alanine aminotransferase (ALT) of 63 U/L (Normal <49 U/L). She was given intravenous doxycycline empirically for suspected Rocky Mountain Spotted Fever. The patient took three days to recover on antibiotics and continued antibiotics for 7 days and confirmatory tests came back positive for Rickettsia rickettsii. A confirmatory indirect immunofluorescence antibody (IFA) assay was performed and IgG antibodies reacted with Rickettsia rickettsii antigen in a serum specimen collected after second admission into the hospital.
- 4. Rocky Mountain Spotted Fever Etiologic agent is Rickettsia rickettsii Transmission is through a tick bite Vectors include: American Dog Tick (Dermacentor variabilis) Rocky Mountain Wood Tick (Dermacentor andersoni) Brown Dog Tick (Rhipicephalus sanguineus) Cayenne Tick (Amblyomma Cajennense) Rarely Lone Star Tick (Amblyomma aureolatum) Symptoms typically begin 2-14 days after a tick bite http://www.cdc.g ov/rmsf/stats/index .html Fatality rate is approximately 20% or higher for untreated patients
- 5. Rickettsia rickettsii Intracellular bacterium Invades eukaryotic cells Pleomorphic, non-motile coccobacilli 0.3 μm by 1.0 μm and weakly gram negative Cannot grow on standard cell culture media Can grow in egg yoke of embryonated eggs and several monoclonal cell culture lines Acquires adenosine triphosphate from host cells Gimenez stain of tick hemolymph cells infected with R. rickettsii http://pathmicro.med.sc.edu/mayer/rocky-bact.jpg
- 7. Pathogenesis Tick bite Phagocytized into endothelial cells Replicate in the cell cytoplasm and nucleus Oxidative and peroxidative injury to cell membrane Leads to vasculitis Erythematous spots Microhemorrhages creating petechial rash
- 8. Pathogenesis continued… Pro-coagulant state Platelet activation Increased fibrinolysis Consumption of anticoagulants Resulting in thrombocytopenia
- 9. Virulence Factors Rickettsial outer membrane protein B (OmpB) – adhesion Endocytosis into the cell Phospholipase D and Hemolysin C Actin based motility by protein RickA Virulence reduced in the winter months Restored by Blood meal or exposure to 37 degree temperatures
- 10. Symptoms 2-14 day incubation period Fever, earliest sign typically above 102ºF Rash (typically occurs 2-5 days after start of fever) Headache (in adults less likely in kids) Nausea Vomiting Abdominal pain (mimicking appendicitis or other causes of acute abdominal pain) Muscle pain Lack of appetite Conjunctival injection (typically in kids) Diarrhea in about 25% of kids
- 11. Laboratory Findings Test Result Complete Blood Count Normal to Increased Platelets decreased Sodium Decreased or normal Hepatic transaminases Mild to moderate increase Serum albumin concentrations Decreased Serum creatinine Increased Blood urea nitrogen Increased
- 12. Diagnosis Immunofluorescent antibody assays Latex agglutination Enzyme-linked Immunosorbant assays Skin biopsy of rash spots for immunohistochemical staining Cell Culture?
- 13. Treatment Doxycycline is the DOC For all ages Adults 100 mg twice daily Children <99 lbs should receive 2.2 mg/kg twice daily Children >99 lbs should receive the adult dosage Duration 7-14 days Chloramphenicol can be used for those with allergies
- 14. Prevention Light colored clothing Long sleeve shirts Long pants tucked into socks Tick repellents Check for ticks Use tweezers to remove tick Keep areas free of high grass and brush
- 15. References "Rocky Mountain Spotted Fever (RMSF)." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 21 Nov. 2013. Web. 28 Apr. 2014. Mahon, Connie R., Donald C. Lehman, and George Manuselis. Textbook of Diagnostic Microbiology. Maryland Heights, MO: Saunders/Elsevier, 2011. Print. Mayer, Gene. "Rickettsia, Ehrlichia, Coxiella and Bartonella." Rickettsia, Ehrlichia, Coxiella and Bartonella. The Board of Trustees of the University of South Carolina, 15 Apr. 2010. Web. 29 Apr. 2014. Woods, Charles R. "Rocky Mountain Spotted Fever in Children." Rocky Mountain Spotted Fever in Children. Pediatric Clinics of North America, n.d. Web. 29 Apr. 2014.
- 16. Questions?
Hinweis der Redaktion
- In early September, an 8 year old female from Tennessee, presented at the emergency room with a fever over 102 for at least two days. She complained of abdominal pain, nausea, diarrhea, and vomiting. The patient was sent home after a diagnosis of viral gastroenteritis. After two days when the patient didn’t get better her parents took her back to the emergency room with fever (unbroken), anorexia, irritability, cough, abdominal pain mimicking appendicitis, conjunctival injection, nausea, diarrhea and vomiting. Physical examination showed a petechial rash on the trunk, arms, legs, palms, and soles as well as hepatosplenomegaly.
- Laboratory results included a WBC count of 11.4 x 109 cells/L; showing increase WBC’s. Thrombocytopenia (72 x 109 platelets/L), elevated aspartate aminotransferase (AST) of 179 U/L (Normal <43 U/L), elevated alanine aminotransferase (ALT) of 63 U/L (Normal <49 U/L). She was given intravenous doxycycline empirically for suspected Rocky Mountain Spotted Fever. The patient took three days to recover on antibiotics and continued antibiotics for 7 days and confirmatory tests came back positive for Rickettsia rickettsii. A confirmatory indirect immunofluorescence antibody (IFA) assay was performed and IgG antibodies reacted with Rickettsia rickettsii antigen in a serum specimen collected after second admission into the hospital.
- Etiologic agent of Rocky Mountain Spotted Fever is Rickettsia rickettsia. Transmission is through a tick bite. The most common vectors include American Dog Tick (Dermacentor variabilis) and the Rocky Mountain Wood Tick (Dermacentor varabilis) Vectors can also be Brown Dog Tick (Rhipicephalus sanguineus) just recently recognized as a vector in Arizona and Mexico as well as the Cayenne tick (Amblyomma cajennense) in Central and south America. The Lone Star Tick is rarely a vector but can be a vector in Central and South America. Rickettsia rickettsii can be found in all life stages of the tick and is only transmitted by adult tick bites and the microbes are released from salivary glands 6-10 hours after feeding. Symptoms typically begin 2-14 days after a tick bite Fatality rate is approximately 20% or higher for untreated patients Treatment reduces risk of death significantly to about 3-6% mortality rate but the CDC reports those numbers have fallen to approximately 0.5% in 2010. Approximately 50% of patients do not remember being bitten by a tick making diagnosis more difficult.
- Intracellular bacterium Invades eukaryotic cells Pleomorphic, non-motile coccobacilli 0.3 μm by 1.0 μm and weakly gram negative Cannot grow on standard cell culture media Can grow in egg yoke of embryonated eggs and several monoclonal cell culture lines Acquires adenosine triphosphate from host cells Ticks harbor Rickettsia rickettsii
- This chart on the left shows the incidence of rocky mountain spotted fever from 2010 per million people. The highest incidence rates are found in Arkansas, Delaware, Missouri, North Carolina, Oklahoma, and Tennessee. The chart on the right shows that the majority of cases also occur in April through September (tick season) but cases have been reported throughout the whole year. Clusters of cases among family members have been seen when the family dog is infected with ticks.
- When a tick bites it releases the organism from the salivary glands. Once the organism is inoculated in the skin by a bite they are phagocytized into endothelial cells and replicate in the cell cytoplasm and nucleus. One article I read suggests that they travel through the lymphatic system and then into blood vessel and then into the endothelial cells but our book reports that they are phagocytized into endothelial cells. Oxidative and peroxidative injury to endothelial cell membranes leads to vasculitis (inflammation of the blood vessels) in internal organs like the brain, heart, lungs and kidneys. The areas of vasculitis in the epidermis creates erythematous spots and progressive injury leads to the microhemorrhages and the petechial rash of the hands, feet, limbs, and trunk. Multi-organ dysfunction due to vascular insufficiency is more likely to cause death than major hemorrhages or vaso-occlusive infarcts (blockages).
- Rickettsia induces a pro-coagulant state which activates platelets, increases fibrinolysis, and consumption of anticoagulants which results in thrombocytopenia. But this does not typically lead to disseminated intravascular coagulation (DIC).
- The rickettsial outer membrane protein B and other microbial surface structures function as adhesions to endothelial cells. The microbe induces local rearrangement of the cells cytoskeleton which leads to endocytosis into the cell. After endocytosis Rickettsia rickettsii lyses the endosome using phospholipase D and hemolycin C. Rickettsia rickettsii grow well in the high potassium concentrations of the cytoplasm of the cell. One very interesting virulence factor is that they can move through the cell by actin based motility which involves recruitment of host cell actin filaments, using protein Rick A, which forms a filamentous comet tail. Rickettsia rickettsii use the actin motility to propel rapidly through the cell and causes a protrusion from the current cell, which creates an invagination of adjacent cell membranes and the cell then engulfs the protrusions into its membrane which allows for intercellular travel without destroying the previous host cell. Virulence is reduced in the winter months and restored upon a blood meal from the tick or by exposure to 37 degrees Celsius.
- 2-14 day incubation period Fever, earliest sign typically above 102ºF Rash (typically occurs 2-5 days after start of fever) Headache (in adults less likely in kids) Nausea Vomiting Abdominal pain (mimicking appendicitis or other causes of acute abdominal pain) Muscle pain Lack of appetite Conjunctival injection (typically in kids) Diarrhea in about 25% of kids
- Complete Blood count is typically normal in the beginning of the disease and increases as time goes on. Platelets are decreased resulting in thrombocytopenia. Decreased sodium levels occur in about 50% of people. Hepatic transaminases like aspartate aminotransferase (AST) and alanine aminotransferase (ALT) have mild to moderate increases. Serum albumin concentrations are typically decreased due to the increased vascular permeability. Serum creatinine and blood urea nitrogen are typically increased due to renal insufficiency in severe disease. Renal insufficiency may be due to vasculitis in the kidney, ischemia-related acute tubular necrosis, or micro-thrombosis.
- Immunoflourescent antibody assays are the best method of detection, however, IgM and IgG increase the most during the second week of infection and are not typically detectable during the first 7 days of illness. Most commercial assays measure both IgM and IgG and a 4 fold rise in antibody titer is considered confirmatory. Another method of detection is a skin biopsy of the rash spots which is helpful during an acute illness. Immunohistochemical staining is approximately 100% specific and 70% sensitive. Blood smears or PCR is not sensitive enough to detect the low levels of organism actually in the blood. A culture will a monoclonal cell line is possible but can only be done in laboratory's that have biosafety level 3 containment procedures, like the Centers for Disease Control and Prevention.
- Doxycycline is the drug of choice for all ages and during the spring and summer months, patients with presentation of fever and headache should be treated before a rash develops. Treatment should begin within the first five days of symptoms before a rash develops for a better prognosis. Meningococcemia and rocky mountain spotted fever can overlap which results in use of a third generation cephalosporin when RMSF is suspected. Adult dosage of doxycycline is 100 mg twice daily and children >99 lbs should receive the adult dosage. Children <99 lbs should receive 2.2 mg/kg twice daily. Doxycycline is prescribed for 7-14 days and it typically takes 24-72 hours for fever to subside. Chloramphenicol can be used for those with allergies to doxycycline. Macrolides and Sulfonamides are not used for treatment because they are not effective. In fact animal studies suggest that use of sulfonamides may increase the severity of illness though an unknown mechanism but might be due to oxidative stress.
- Prevention methods include wearing light colored clothing, so that attached ticks are more easily noticed and wearing long sleeved shirts and long pants and tucking pant legs into socks. Tick repellents can also be used to prevent tick attachment. Those that live in endemic areas and have been outside for a significant amount of time to check for ticks after coming inside. Knowing that you have been bitten by a tick when you start a high fever will speed up the clinical diagnosis and give a favorable prognosis. When trying to remove ticks use tweezers by pulling gently but firmly. Do not pull too fast or the tick head will detach from the body and remain in the skin. Try to keep areas around homes free of high grass and brush to reduce tick habitat.