Atypical Bacteria 2 2024 PDF

Atypical Bacteria-2: The Rickettsiales Atypical Bacteria Intracellular Extracellular Chlamydia Legionella Mycobacterium Mycoplasma...

Atypical Bacteria-2: The Rickettsiales Atypical Bacteria Intracellular Extracellular Chlamydia Legionella Mycobacterium Mycoplasma Spirochetes Rickettsiales Leptospira Borellia Treponema Recommended Reading and Learning Objectives Recommended reading: appropriate chapters or sections from Medical Microbiology; Murray et al on line-in library With regard to each pathogen species describe: Microbiological features- nature of cell wall, intra- or extracellular where are they found in nature (are they strict human pathogens, or do they infect animals, or are they found in soil, etc) how they are transmitted- ie, how do we become infected the clinical manifestations of the diseases they cause, and be able to recognize a description of the disease in a test question the pathogenesis of diseases they cause, being sure to relate bacterial virulence factors to the pathogenesis if discussed Diagnostic features- how is an etiologic diagnosis made how these infections can be prevented (ie, vaccine availability or behavioral modification, etc) Be able to define all terms in the ppt, including, but not limited to those in red. If you cannot do this from the lecture, you must look them up. Answer all questions posed in the ppt.  Organisms and diseases discussed in this lecture Rickettsial Diseases: Rickettsia rickettsii- Rocky Mountain Spotted Fever (RMSF) Rickettsia prowazekii- Louse-Borne (Epidemic Typhus) Rickettsia typhi- Flea-Borne Typhus (Endemic Typhus) Orientia tsutsugamushi -Mite-Borne Typhus (Scrub Typhus) Anaplasma sp- Anaplasmosis Ehrlichea sp- Ehrlichiosis Rickettsia spp Obligate intracellular bacteria Frequent endosymbionts of ticks and other blood-sucking, and non-blood sucking arthropods Do not Gram stain, however, have a Gram-negative cell wall In humans, often replicate in endothelial cells  Case An 8-year-old boy in North Carolina developed fever, severe headache, myalgia, nausea and vomiting for several days, followed by the rash shown in the photo. About 1 week prior to the onset of his illness, he had been hiking with his cub scout troop and the organism shown was removed from his scalp the day after the hike. What kind of organism was removed from his scalp? What disease does this boy have? How is this pathogen maintained in nature? Where dies this disease occur (focus of infection) What are the potential consequences if this disease is not diagnosed RMSF Epidemiology- Rickettsia rickettsii- maintenance of the infection in nature and incidental spread to humans Spotted-fever-group rickettsiae are maintained in nature primarily by transovarial and trans-stadial transmission in ticks. Rodents may also play a role by transiently developing a sufficient number of organsims in the blood to infect a feeding tick. Humans are incidentally infected and do not maintain the organism in nature.  Epidemiology-2: Vectors and Foci of Infection Despite the name, RMSF (and other spotted fever rickettsial diseases) occur most commonly east and central US Vector in eastern and central US is Dermacentor variabilis. Different vector species in different regions- see notes pages Pathogenesis-1: Replication and consequences of Rickettsia rickettsii in endothelial cells Rickettsia are obligate intracellular organisms infecting human endothelial cells. Enter cells via interaction with specific host molecule on membrane and inducing the cell to phagocytose it into a vesicle. They escape from the phagosome, replicate and spread to other cells by hijacking actin filaments. They use the actin like a rubber band to shoot themselves from one cell to the next. Result- endothelium is compromised, leading to petechial rash on skin and loss of fluid and protein from blood leading to edema, hypovolemia, hypotension, and hypoalbuminemia. Clinical Manifestations-1 Incubation period 3-12 days Major initial symptoms (=prodrome) include fever >102F, severe headache, chills, malaise, myalgia Nausea, anorexia, photophobia are also common After ~ 5 days of initial symptoms, classic rash develops on most people. Characteristics of rash are very important!!! begins on ankles and wrists spreads to palms and soles (a very unusual site for a rash!) Also spreads to arms, legs, trunk but not face Rash consists of small (1-5mm) pink macules More pictures of RMSF rash Clinical Manifestations-2 Diseases progresses rapidly of not recognized and treated By the time rash appears, already advanced Vascular injury can lead to lung, heart GI, renal and nervous system damage Inflammation and damage to the blood vessels and capillaries can induce blood clots throughout the body Case fatality rate as high as 30% in untreated; 4% in hospitalized patients Diagnosis and Treatment Diagnosis made by: PCR in first week of symptom onset Acute and convalescent antibody titers after first week of symptom onset Measure antibodies to the agent when patient is sick (acute sample) Measure again 2-4 weeks later (convalescent sample) Antibody titer must rise 4 fold to be diagnostic Diagnosis of RMSF FYI Treatment- doxycyclin Other rickettsial diseases- Epidemic Typhus aka Louse-borne Typhus Agent- Rickettsia prowazekii Vector- body louse Reservoir- humans Once common disease, now rare. Can occur when people are housed in overcrowded, unsanitary conditions such as refugee camps Outbreaks of epidemic typhus have occurred in homeless populations in US Organism infects endothelial cells High fever, chills, headache, rash with sequalae similar to RMSF if untreated Case-fatality rate 60% without treatment Treatment- doxycyclin Other rickettsial diseases- Endemic Typhus aka Flea-Borne Typhus Agent- Rickettsia typhi Vector- fleas Reservoir- rats, opossum, cats May be more common than expected in US among homeless populations Clinical manifestations: replicates in endothelial cells, causes high fever, severe headache, chills, myalgia, petechial rash on chest, back, arms and legs Self-limiting disease Treatment- doxycycline Other rickettsial diseases-Scrub Typhus Agent- Orientia tsutsugamushi Vector- Trombiculid mites (chiggers- but not the ones around here!) Reservoir- rodents (rats, others) Most cases of scrub typhus occur in rural areas of Southeast Asia, Indonesia, China, Japan, India, and northern Australia. Clinical manifestations: replicated in endothelial cells, causes high fever, severe headache, chills, myalgia, petchial rash Untreated cases can lead to multiple organ failure FYI Treatment- doxycyclin Brain Break Compare the rickettsial diseases we just covered in terms of- think about how you would tell them apart in a case-based question! Name of disease Reservoir Vector Focus of infection Clinical manifestations Ehrlichiosis and Anaplasmosis Case A 72-year-old man from NE Oklahoma was admitted to the hospital with a 2 day history of fever, chills, headache, myalgias, diarrhea and confusion. After admission, he had respiratory failure requiring intubation. Laboratory data revealed: decreased white cell count, reduced hemoglobin, elevated liver function tests, alterations in blood clotting and kidney function abnormalities. Chest x-ray, blood and urine cultures and lumbar puncture were all negative. Serologies for influenza A and B, Rickettsia typhi IgM, Rocky Mountain spotted fever, Lyme PCR, and Anaplasmosis PCR were all negative; however an Ehrlichia PCR came back positive and confirmed the diagnosis of human myelocytic ehrlichiosis (HME). His blood smear showed the typical dispersed intracytoplasmic inclusions of HME seen in monocytes Ehrlichia spp Taxonomically related to Rickettsia (in same Rickettsiales group) Obligate intracellular bacteria Do not pick up Gram stain, but have a Gram-negative cell wall Pathogens: Ehrlichia chaffeensis; E. canis Vector: Ticks- Amblyomma americanum and Rhipicephalus sanguineus Reservoir- deer, canids (see next slide) Epidemiology of Ehrichiosis- Maintenance of the pathogens in nature and incidental spread to humans Enzootic cycle Primary reservoir is white tailed deer, although many large and small mammals may also play role Vector is tick Abmlyomma americanum (Lone star tick) or Rhipicephalus sanguineus (brown dog tick) Epidemiology of Ehrlichiosis-2: Focus of Infection Pathogenesis of Ehrlichiosis Pathogen enters blood with bite of infected tick Infect monocytes/marcophages by inducing phagocytosis Replicate within membrane-bound vesicles called morula Leave the cell following cell lysis or exocytosis Tissues with greatest burden of pathogen include liver, spleen, lymph nodes, bone marrow, lung, kidney, and CNS Clinical Manifestations, Diagnosis and Treatment of Ehrlichiosis Symptoms begin 1-2 weeks following tick bite and include: Sudden high fever, severe headache, malaise, chills, nausea, vomiting, anorexia Rash may occur, especially in children Laboratory findings may include leukopenia, thrombocytopenia and anemia If not treated, can progress to sepsis with damage to multiple organs Diagnosis and Treatment of Ehrlichiosis Diagnosis PCR or acute and convalescent antibody titers Finding morulae in cytoplasm of monocytes is insensitive, but aids in diagnosis when found FYI Treatment Doxycycline  Case Two weeks after returning from a camping vacation in Cape Cod, MA, a 58 year old man presented to his primary care physician with six days of fatigue, severe headache, fever, chills, arthralgia, myalgia and mild right upper quadrant pain. Clinical workup revealed leukopenia, thrombocytopenia, and elevated transaminases. His preliminary workup was also negative for Lyme antibody, EBV and CMV IgM, and viral hepatitis markers. At no point did the patient notice a skin rash or a tick anywhere on his person. Diagnosis was made following PCR of blood. A peripheral blood smear was also done and is shown. What is the diagnosis? Anaplasma/Anaplasmosis Taxonomically related to Rickettsia (in same Rickettsiales group) Obligate intracellular bacteria Do not pick up Gram stain, but have a Gram-negative cell wall Pathogen: Anaplasma phagocytophilum Vector: Tick- Ixodes scapularis in east and midwest Reservoir- several small and large mammalian species- both wild and domestic Epidemiology of Anaplasmosis (and comparison with Ehrichiosis)- Maintenance of the pathogens in nature and incidental spread to humans Pathogen enters blood with bite of infected tick Infect neutrophils by inducing phagocytosis Replicate within membrane-bound vesicles called morula Leave the cell following cell lysis or exocytosis Tissues with greatest burden of pathogen include liver, spleen, lymph nodes, bone marrow, lung, kidney, and CNS Epidemiology of Anaplasmosis- Focus of Infection (and comparison with Ehrlichiosis) Geographic range of Ehrlichiosis Anaplasma – range overlaps with Lyme Disease Vector is the same for both diseases Co-infection with both organisms is not uncommon Pathogenesis of Anaplasmosis (and comparison with Ehrlichiosis) Pathogen enters blood with bite of infected tick Infect neutrophils (Anaplasma) or monocytes (Ehrlichia) by inducing phagocytosis Replicate within membrane-bound vesicles called morula Leave the cell following cell lysis or exocytosis Frequent laboratory abnormalities similar to Ehrlichiosis: include thrombocytopenia, leukopenia, anemia and elevated hepatic transaminase levels In addition to common manifestations (shown in case), a minority of patients can manifest organ-specific symptoms involving the GI, respiratory and nervous systems Diagnosis and Treatment of Anaplasmosis Diagnosis PCR or acute and convalescent antibody titers Finding morulae in cytoplasm of neutrophils is insensitive, but aids in diagnosis when found FYI Treatment Doxycycline Summary Points Compare the Rickettsiales- Rickettsia sp and Ehrlichia and Anaplasma with Borellia burgdorferi in terms of: Reservoir Vector Focus of infection Clinical manifestations Diagnostic findings Treatment (even though it is FYI- they are all treated with the same drug)