Microbiology Flashcards
Cysticercosis vs. taeniasis.
Taenia solium, a tapeworm, causes disease endemically in Mexico, Central and South America, Asia, and Africa. Cysticercosis occurs during an infection by the larval stage of T solium when ova are ingested. The ova develop into larvae, penetrate the intestinal wall, disseminate throughout the body via the vascular system, and encyst in tissue as cysticerci. Cysticerci have a propensity for developing in the CNS (60% of cases). Alternatively, taeniasis occurs during an infection by the adult tapeworm of T solium when the human definitive host ingests cysticerci. The cysticerci evaginate, attach to the intestinal wall, and develop into sexual mature cestodes.
In what 3 situations can asymptomatic bacteriuria be diagnosed?
- In asymptomatic women, 2 consecutive voided urine specimens with isolation of the same bacterial strain in quantitative counts of >10^5 cfu/mL. 2. In asymptomatic men, a single voided urine specimen with isolation of a single bacterial species in a quantitative count of >10^5 cfu/mL. 3. In men and women, a single catheterized specimen with a single bacterial species in a count of >10^2 cfu/mL.
Hemorrhagic cystitis due to adenoviruses, especially type 11, is most often seen in (type of patient).
Hemorrhagic cystitis due to adenoviruses, especially type 11, is most often seen in bone marrow transplant recipients.
The most common cause of acute infectious diarrhea is ___.
Viruses, especially noroviruses (calicivirus, Norwalk virus), enteric adenoviruses, and rotavirus. These agents account for at least 50% of community-acquired acute infectious diarrhea. And if there is nothing unusual in the history, such as hospitalization, antibiotic use, or travel, these agents cause 80-90% of cases.
What bacterium is the most commonly identified cause of Guillain-Barre syndrome?
C. jejuni, most commonly type O:19, is the most commonly identified cause, implicated in ~30% of cases.
The syndrome of cholera is caused principally by what two serogroups of V. cholerae?
Serogroup O1 and serogroup O139. Noncholera (non-01 and non-139) strains may cause less severe gastroenteritis and/or wound infections.
What 2 bacterial organisms can cause an HLA-B27-linked post-infectious arthritis?
C. jejuni and Y. enterocolitica can cause the development of a reactive arthropathy (so-called enteropathic arthritis) in persons with HLA-B27.
What are the HACEK organisms?
Haemophilus (H. parainfluenzae, H. aphrophilus, H. paraphrophilus), Actinobacillus (A. actinomycetemcomitans, Aggregatibacter aphrophilus), Cardiobacterium hominis, Eikenella corrodens, Kingella kingae. These are all slow growing Gram negative bacteria that form part of the normal oropharyngeal flora. They account for 5-10% of infective endocarditis involving native valves, are the most common Gram negative cause of endocarditis among non-IVD users, and are a frequent cause of culture-negative endocarditis. In addition to valvular infections in the heart, they can also produce other infections such as bacteremia, abscess, peritonitis, otitis media, conjunctivitis, pneumonia, arthritis, osteomyelitis, and periodontal infections.
HSV 1 is a common cause of (encephalitis and/or meningitis), and HSV 2 is a common cause of (encephalitis and/or meningitis). The best way to diagnose both of these is ___.
HSV 1 is a common cause of encephalitis, and HSV 2 is a common cause of meningitis. The best way to diagnose both of these is CSF PCR.
Erysipelas is caused by (organism). Erysipeloid is caused by (organism).
Erysipelas is caused by S. pyogenes. Erysipeloid is caused by Erysipelothrix rhusiopathiae.
Adiaspiromycosis is caused by (organism).
Adiaspiromycosis is caused by Chrysosporium parvum.
Coxsackie A virus causes (conditions). Coxsackie B virus causes (conditions).
Coxsackie A virus causes hand-foot-mouth disease and herpangina. Coxsackie B virus causes myocarditis, pericarditis, and epidemic pleurodynia (the grippe).
What is the vector for B. burgdorferi?
The Ixodes tick. I. dammini (scapularis?) (AKA blacklegged ticks or deer tick) in the Eastern US, I. pacificus (AKA western blacklegged tick) in the Western US, I. ricinus (AKA sheep tick or castor bean tick) in Europe, and I. persulcatus (AKA taiga tick) in China. The natural reservoir is the white-footed mouse, but in endemic areas, deer are an important reservoir.
Polyoma viruses include the ___ virus and ___ virus. Both are typically acquired in childhood and enter latency, supposedly within the ___ and ___. If immunosuppression occurs, viral reactivation may lead to the development of progressive multifocal leukoencephalopathy due to ___ virus or ___ virus-induced hemorrhagic cystitis.
Polyoma viruses include the JC virus and BK virus. Both are typically acquired in childhood and enter latency, supposedly within the brain and urothelium. If immunosuppression occurs, viral reactivation may lead to the development of progressive multifocal leukoencephalopathy due to JC virus or BK virus-induced hemorrhagic cystitis. BK virus causes the appearance of decoy cells within urine cytology, with the characteristic smudgy nuclear inclusions and lack of the usual chromatin detail as seen in CIS. Similar inclusions are seen within oligodendroglial cells in the demyelinative lesions of PML.
What HPV types (in order of frequency) are seen mostly commonly in the following lesions? Plantar wart, common wart, flat (juvenile) wart, oral squamous papilloma, oral focal epithelial hyperplasia (Heck disease), epidermodysplasia verruciformis, laryngeal papillomas, condyloma acuminatum, cervical LSIL, cervical HSIL, cervical AIS and invasive cervical adenocarcinoma.
Plantar wart: 1, 2. Common wart: 2, 1, 4, (HPV 7 in fish and meat handlers). Flat (juvenile) wart: 3, 10. Oral squamous papilloma: 6, 11. Oral focal epithelial hyperplasia (Heck disease): 13, 32. Epidermodysplasia verruciformis: 2, 3, 10, 5, 8. Laryngeal papillomas: 6, 11. Condyloma acuminatum: 6, 11. Cervical LSIL: 6, 11. Cervical HSIL: 16, 18, 31, 33, 35. Cervical AIS: 18. Invasive cervical adenocarcinoma: HPV 16 and 18 are detected with equal prevalence in most subtypes of cervical adenocarcinoma.
What are some organisms that stain AFB+?
Mycobacteria, Nocardia, Corynebacteria, Cryptosporidium, Microsporidium, Isospora, Cyclospora, Sarcocystis, Legionella micdadei, Rhodococcus equi, Saccharomyces.
What are the differences between the Ziehl-Neelsen, Kinyoun, and Fite acid-fast stains?
The acid-fast stains are based on the ability of certain organisms to retain the red dye carbol fuchsin despite acidic decolorization. The carbol fuchsin stain is a mixture of fuchsin with phenol (carbolic acid). In the Ziehl-Neelsen technique, heat is used to aid penetration of the carbol fuchsin, and a strong acid (3% HCl) is used for decolorization. The Kinyoun technique is a “cold” technique; heat is not applied; instead, a detergent is used to aid penetration of the dye. The Fite technique is a modified acid-fast stain, where a weaker acid such as 1% H2SO4 is applied instead of HCl for decolorization. Bacteria that are not acid-fast by the Ziehl-Neelsen technique, such as Nocardia and M. leprae, may be acid-fast with the Fite technique (cells with a thin capsule, as may be the situation with many rapidly growing strains, are more susceptible to decolorization, so weaker acid will not decolorize as much). Also, the Ziehl-Neelsen technique may be more sensitive than the Kinyoun technique in detecting lightly staining organisms, since the Kinyoun technique may cause easier decolorization.
How are the tube coagulase test, slide coagulase test, and commercial latex agglutination test different in ability to identify S. aureus?
The tube coagulase test tests for free/secreted coagulase; it is a definitive ID for S. aureus and the gold standard. But you need to incubate the plasma + colony for 24 hours to call it negative. The slide and latex agglutination tests test for bound coagulase/cell-bound coagulase/clumping factor; they are quicker tests but may not always differentiate S. aureus from coag-negative Staph.
MRSA strains produce an altered penicillin-binding protein, ___, which is encoded by the gene ___.
MRSA strains produce an altered penicillin-binding protein, PBP 2a, which is encoded by the gene mecA.
Macrolide-resistant isolates of S. aureus come in what 2 classes?
Macrolides include erythromycin. Lincosamides include clindamycin. 1. Those that demonstrate constitutive or inducible clindamycin resistance. Is referred to as MLS B resistance (affects macrolides, lincosamides, and type B streptogramins). The mechanism is target modification - methylation of 23S rRNA. 2. Those that are resistant only to macrolides. The mechanism is efflux.
What enzyme does C. perfringens produce that differentiates it from the other Clostridium species?
Lecithinase. Evident on egg yolk agar and lecithin lactose agar.
A double zone of hemolysis is characteristic of what organism?
C. perfringens.
Which Plasmodium spp are associated with fever spikes every 48 hours, and which are associateed with fever spikes every 72 hours?
Fever spikes every 48 hours (tertian fever) characterize P. ovale, P. vivax, and P. falciparum. Due to its lethality, P. falciparum is also called “malignant tertian malaria”. P. ovale and P. vivax are also known as “benign tertian malaria”. Fever spikes every 72 hours (quartan fever) characterizes P. malariae.
Which Plasmodium spp are associated with: Nephrotic syndrome? CNS involvement? True disease relapse? Recrudescence?
Nephrotic syndrome is associated with P. malariae. CNS involvement is associated with P. falciparum. True disease relapse is seen only with P. vivax and P. ovale. Recrudescence is possible with any of the species.
Which Plasmodium spp infect younger RBCs, older RBCs, and any RBCs?
P. vivax and P. ovale infect younger erythrocytes (this is why the infected erythrocytes appear enlarged). P. malariae infects older erythrocytes. P. falciparum infects any erythrocytes.
Explain disease relapse and recrudescence with malaria.
True disease relapse is seen with P. vivax and P. ovale only, and results from the harboring of latent sporozoites = hypnozoites within the liver. Neither transfusion-transmitted disease nor transplacental infection is associated with relapse. Recrudescence results from a rebound of persisting (though depleted to levels that are undetectable) blood forms to clinically detectable levels.
Describe the eggs of Taenia saginata (beef tapeworm) and Taenia solium (pork tapeworm).
The diagnosis is usually made by findings eggs in stool. The eggs of T. saginatum and T. solium are identical. They are 30-40 um, spherical, have a thick radially striated wall, and contain 3 pairs of hooks. The finding of such eggs is reportable as “Taenia species” only. Further characterization relies upon the differences in the scolex or proglottid. The scolex of T. saginata has 4 suckers and a smooth surface (unarmed rostellum); each proglottid is elongated and has >13 lateral uterine branches. The scolex of T. solium has 4 suckers and many tiny hair-like hooks on the surface (armed rostellum); each proglottid is short and has <13 lateral uterine branches. The eggs of T. saginata are not infectious to humans; thus, unlike T. solium, cysticercosis due to T. saginata does not occur.
The eggs of (T. saginata or T. solium) are not infectious to humans.
The eggs of T. saginata are not infectious to humans. Hence, unlike T. solium, cysticercosis due to T. saginata does not occur.
What are the differences in geographic distribution, primary and secondary disease sites, appearance in culture, and appearance in tissue for Histoplasma capsulatum var capsulatum and Histoplasma capsulatum var duboisii?
Var capsulatum is found worldwide; in the US, it is found in the Ohio and Mississippi river valleys. Var duboisii is found in Africa. Var capsulatum causes primary pulmonary and mediastinal disease, then disseminates to reticuloendothelial system. Var duboisii causes primary pulmonary and mediastinal disease, then disseminates to skin and bone. In culture, var capsulatum is a hyaline septate mold with lollipop-like smooth microconidia and spiked macroconidia. In culture, var duboisii is indistinguishable from var capsulatum. In tissue, var capsulatum has 2-5 um budding yeasts. In tissue, var duboisii has 10-15 um thick-walled budding yeasts.
What are the appearances of the yeast and mold forms of: Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Sporothrix schenckii, and Paracoccidioides braziliensis?
H. capsulatum yeast form is 2-5 um with narrow-based budding; mold form is hyphae with periodic lollipop-like microconidia and spiked macroconidia. C. immitis yeast form is 50-200 um spherules with 2-5 um nonbudding endospores; mold form is barrel-shaped arthroconidia. B. dermatitidis yeast form is 8-12 um with broad-based budding; mold form is hyphae with lollipops. S. schenckii yeast form is 2-5 um elongated (cigars) with narrow-based budding; mold form is daisy heads. P. braziliensis yeast form is 10-15 um mariner’s wheel budding; mold form is hyphae with lollipops.
What are the hyalinohyphomyces?
The septate hyaline molds other than the dermatophytes and Aspergillus spp. They can be grouped together as the hyalinohyphomyces due to their shared clinical significance. They include: Acremonium, Beuveria, Chrysosporium, Fusarium, Gliocladium, Pseudoallescheria, Penicillium, Paecilomyces, Scedosporium, Scopulariopsis, and Sepedonium. Hyalohyphomycosis is a term that refers to invasive fungal infections caused by hyaline septate molds that have not been further speciated.
Malassezia furfur. In KOH preps of skin scrapings and in histologic sections of affected skin, M. furfur appears as ___. In culture, M. furfur grows as yeasts in just a few days on Saboraud medium when appropriately cultured: ___.
Malassezia furfur. In KOH preps of skin scrapings and in histologic sections of affected skin, M. furfur appears as short hyphae and spherical yeasts. This “spaghetti and meatballs” or “frankfurters and meatballs” appearance distinguishes it from the usual hyphae-only appearance of typical dermatophytes. In culture, M. furfur grows as yeasts in just a few days on Saboraud medium when appropriately cultured: at 35 C and overlaid with olive oil.
What are Henderson-Patterson bodies?
Henderson-Patterson bodies = molluscum bodies, seen in molluscum contagiosum. They are eosinophilic intracytoplasmic inclusion bodies (accumulated virus particles) in keratinocytes of stratum spinosum and stratum granulosum.
What is myospherulosis?
Myospherulosis, AKA spherulocytosis AKA subcutaneous spherulocystic disease, is an iatrogenic benign mass formed by a foreign body-type granulomatous reaction to lipid-containing material and blood. Clinically, there are solid subcutaneous or dermal nodules. Grossly, is a large saccular cyst-like lesion Histologically, there are saclike structures with fungi-like spherules. The spherules are composed of erythrocytes damaged by endogenous and exogenous fat. The damaged erythrocytes are enclosed by a lipid membrane and later phagocytosed by histiocytes as part of the lipogranulomatous reaction that takes place in adipose tissue. The walls of the spherules are formed due to the physical emulsion phenomenon that occurs between lipid-containing materials and blood. Myospherulosis can be a result of fat necrosis, malignancy such as RCC, endogenous membranocystic degeneration of fat that occurs in lupus, or lipid/petrolatum-based medications being injected or applied to open wounds. It is called MYOspherulosis due to the involvement of skeletal muscle in some patients. It can be mistaken for true fungus, such as Coccidioides, because myospherulosis has parent bodies/pigmented bodies and spherules/endobodies that are similar in size and morphology to Coccidioides; however, myospherulosis has pigmented bodies, while Coccidioides is never pigmented.
What are the 3 main types of multinucleated giant cells?
Foreign body giant cells, Langhans giant cells, and Touton giant cells. All three types are transformed macrophages; mononuclear phagocytes fused under the influence of cytokines. Foreign body giant cells have nuclei that are randomly distributed but often aggregate as centrally located, overlapping nuclei. Langhans giant cells have a peripheral ring-like arrangement of nuclei in an arcuate configuration but no rim of clear cytoplasm. Touton giant cells have a ring of nuclei separating a peripheral clear or foamy rim of cytoplasm from central, more eosinophilic cytoplasm. The peripheral cytoplasm appears clear due to high lipid content. Touton giant cells are seen in lesions with high lipid content, such as xanthomas, xanthogranulomas, and fat necrosis. Touton giant cells can also be seen in dermatofibroma. Other types of multinucleated giant cells include epithelium-derived MGCs, which can be prominent in certain viral infections such as measles (Warthin-Finkeldey cells), RSV, HSV/VZV, and parainfluenza. Also, MCGs derived from neoplastic cells may be formed in a variety of neoplasms.
What is spirochetosis?
Human intestinal spirochetosis is defined histologically by the presence of spirochetal microorganisms attached to the apical cell membrane of colorectal epithelium. Human intestinal spirochetes include Brachyspira aalborgi and Brachyspira pilosicoli. Incidence is common in poorly developed areas, but low where living standards are high. Homosexuals and HIV+ individuals are at high risk. Most patients are asymptomatic, but children, homosexual and HIV+ men are more likely to be symptomatic regardless of invasion. The bacteria can be highlighted using silver stains, PAS, Giemsa, Alcian-blue (pH 2.5) and by immunohistochemistry. Intestinal spirochetosis often coexists with other enteric pathogens, including Entamoeba histolytica, Enterobius vermicularis, Helicobacter pylori, Shigella flexneri and Neisseria gonorrhoeae.
What are the histologic differences between HHV8-negative and HHV8-positive plasma cell variant cases of Castleman’s disease?
HHV8-negative plasma cell variant of CD is characterized by large sheets of mature plasma cells expanding interfollicular regions. While plasma cells are usually polyclonal, a subset of cases shows monoclonal plasma cells; these plasma cells are usually lambda light chain restricted. A subset of follicles may have hyaline vascular-like features; though, these features are often less distinct than in hyaline vascular CD. The HHV8-positive plasma cell variant of CD has interfollicular areas expanded by large sheets of mature, immature, and/or atypical plasma cells. These cases can have increased numbers of plasmablasts in the follicle mantle zones, and a subset of them evolves into HHV8-positive plasmablastic lymphoma.
What is IPSID?
ImmunoProliferative Small Intestinal Disease is a rare disorder that is considered a variant of MALT lymphoma with nearly complete plasmacytic differentiation. Its name results from its preferential involvement of the small intestine, but it is also known as IgA heavy chain disease, because the neoplastic cells in about one-half of cases produce an abnormal, truncated IgA heavy chain that is missing the variable and the first constant regions and that can be found in the serum. The plasma cells will be positive for CD138 but negative for kappa and lambda light chains. IPSID is suspected to result from Campylobacter infection, and early cases have a relatively high rate of response to broad-spectrum antibiotics. Although it was thought that IPSID was entirely an inflammatory process, it has been now confirmed as a clonal process. It is relatively common for IPSID to progress to a high-grade lymphoma indistinguishable from DLBCL.
Chromoblastomycosis is also called ___.
Chromoblastomycosis is also known as “Chromomycosis,” “Cladosporiosis,” “Fonseca’s disease,” “Pedroso’s disease,” “Phaeosporotrichosis,” and “Verrucous dermatitis.” It is a long-term fungal infection of the skin and subcutanous tissue (a chronic subcutaneous mycosis). The infection occurs most commonly in tropical or subtropical climates, often in rural areas. It is caused by specific types of dematiaceous fungi which become implanted under the skin, often by thorns or splinters. The term chromoblastomycosis is restricted to the cases in which sclerotic cells/Medlar bodies/chromo bodies (an adaptive tissue form of the fungi) are present in tissue.
What fungi cause chromoblastomycosis?
Chromoblastomycosis is a chronic fungal infection of the skin and the subcutaneous tissue caused by traumatic inoculation of a specific group of dematiaceous fungi (usually Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporium carrionii, or Fonsecaea compacta) through the skin. Exophiala species may also be part of the group. The term chromoblastomycosis is restricted to the cases in which sclerotic cells/Medlar bodies/chromo bodies (an adaptive tissue form of the fungi) are present in tissue.
What are Medlar bodies?
Medlar bodies, also called chromo bodies, are the adaptive tissue form (“sclerotic cells”) of a specific group of dematiaceous fungi that cause chromoblastomycosis. They are round, brown, thick-walled structures that are 4-12 µm in diameter, resembling overlapping copper pennies. They divide by septation, resembling hot-cross buns.
What is peliosis hepatis?
Peliosis hepatis is characterised by randomly distributed multiple blood-filled cavities throughout the liver. The size of the cavities usually ranges between a few millimeters to 3 cm in diameter. The pathogenesis of peliosis hepatis is unknown. There are several hypotheses as to cause: it arises from sinusoidal epithelial damage, from increased sinusoidal pressure due to obstruction in blood outflow from the liver, or from hepatocellular necrosis. The condition is typically asymptomatic and is discovered following evaluation of abnormal liver function tests. However, when severe it can manifest as jaundice, hepatomegaly, liver failure and hemoperitoneum. Disease associations include… Infections: HIV, Bacillary peliosis (caused by Bartonella), Staphylococcus aureus. Chronic conditions: End stage renal failure, Kwashiorkor, tuberculosis and other chronic infections. Malignancy: Monoclonal gammopathies, Hodgkin disease, malignant histiocytosis, seminoma, hepatocellular adenoma, hepatocellular carcinoma. Renal transplants: It can be found in up to 20% patients, can be related to azathioprine or cyclosporine use, and may be associated with increased risk of transplant rejection. Drugs and toxins: Corticosteroids, androgens, azathioprine, tamoxifen.
Kaposi sarcoma overview.
Kaposi sarcoma (KS) is a low-grade vascular tumor associated with Kaposi sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8) infection. Kaposi sarcoma lesions predominantly present at mucocutaneous sites, but may involve all organs and anatomic locations. Recognized epidemiologic-clinical forms of KS include classic, African (endemic), AIDS-associated (epidemic), and iatrogenic KS. New clinical manifestations have been described, such as antiretroviral therapy–related KS regression or flares. Kaposi sarcoma lesions evolve from early (patch stage) macules into plaques (plaque stage) that grow into larger nodules (tumor stage). Newer histologic variants include anaplastic, hyperkeratotic, lymphangioma-like, bullous, telangiectatic, ecchymotic, keloidal, pyogenic granuloma–like, micronodular, intravascular, glomeruloid and pigmented KS, as well as KS with sarcoidlike granulomas and KS with myoid nodules. Latency-associated nuclear antigen (HHV8) is the most specific immunohistochemical marker available to help distinguish KS from its mimics. KS remains one of the most common AIDS-defining malignancies.
Kaposi sarcoma pathogenesis.
With the advent of genomic technologies, proliferating KS spindle tumor cells are now known to be of endothelial origin, confirming former studies that used histochemistry and ultrastructural findings. Circulating blood mononuclear and endothelial “progenitor cells” are believed to be the source of early KS lesions. Infection with HHV8 reprograms the host’s blood endothelial cells so that they resemble lymphatic endothelium, upregulating several lymphatic-associated genes such as lymphatic vessel endothelial receptor 1 (LYVE1), podoplanin, and vascular endothelial growth factor receptor 3 (VEGFR3). However, HHV8 infection alone appears to be insufficient for the development of KS. Kaposi sarcoma progression relies also on some degree of host immune dysfunction and the local inflammatory milieu. Kaposi sarcoma growth involves the upregulation of many key HHV8 gene products, such as the latency-associated nuclear antigen (LANA-1 or LNA-1). Like other herpesviruses, HHV8 remains latent within cells and has developed a variety of mechanisms to evade the host immune system.
Iatrogenic KS is associated with immunosuppression due to drugs or after transplantation. Kaposi sarcoma occurs mainly in ___ transplant recipients, and infrequently after other solid organ or bone marrow transplants.
Iatrogenic KS is associated with immunosuppression due to drugs or after transplantation. Kaposi sarcoma occurs mainly in renal transplant recipients, and infrequently after other solid organ or bone marrow transplants. Posttransplant KS may result from reactivation of latent HHV8 infection in recipients or from tumor cells contributed from organ donors. Transplant-associated KS has a protracted, but aggressive course. In transplant recipients, KS lesions may regress after discontinuation of immunosuppressive therapy.
For the 4 types of Kaposi sarcoma, list the epidemiology, clinical distribution, and behavior.
Classical type: Mainly males aged 40-70 years, of Mediterranean or Jewish Ashkenazi origin. Skin of the lower extremities, but mucosal and visceral lesions may develop. Indolent. African type: Middle-aged black adults and children from equatorial Africa. Multiple localized skin tumors, involving lower extremities and/or lymph nodes. Progressive; lymphadenopathic form is aggressive. AIDS-associated type: Mainly homosexual males and IVDUs aged 20-50 years; now equally affects women and children in Africa. Disseminated mucocutaneous and visceral involvement. Aggressive; lesions may regress or flare with initiation of antiretroviral therapy. Iatrogenic type: Immunosuppressed persons of any age from autoimmune disease, drugs, or transplantation. Localized mucocutaneous or disseminated KS, with possible visceral lesions. Variable; may regress after immunosuppression is discontinued.
Histologic appearance of Kaposi sarcoma.
Early patch-stage KS is characterized by abnormal vessels lined by thin endothelial cells dissecting the dermis. Ramifying proliferating vessels often surround larger ectatic vessels and skin adnexa, producing the so-called promontory sign. This sign is not pathognomonic for KS, as it has also been described in other vascular lesions including benign vascular tumors and angiosarcoma. Sparse chronic inflammatory cells, extravasated red blood cells, and hemosiderin-laden macrophages are frequently present in patch KS lesions. These early histologic changes may be inconspicuous, and for that reason can be easily missed on biopsy. Plaque-stage KS lesions are characterized by a proliferation of both spindle cells and vessels, which in the skin involve most of the dermis, and sometimes even the subcutis. Well-developed KS tumors consist of several fascicles of these spindle-shaped tumor cells, often admixed with a variable chronic inflammatory infiltrate composed of lymphocytes, plasma cells, and dendritic cells. Kaposi sarcoma lesions also contain several hemosiderin-laden macrophages. Iron staining may help distinguish KS from similar-appearing interstitial granuloma annulare lesions that lack iron. In cross section, KS nodules display a sievelike appearance caused by the transection of spindle cells with intervening slitlike spaces. Eosinophilic and PAS–positive hyaline globules are a common finding in advanced KS lesions. These globules may be located within lesional cells or extracellularly. Typical KS lesions are devoid of marked cellular pleomorphism, necrosis, or a significant number of mitotic figures. In rare instances, AIDS-KS lesions may harbor concomitant pathologic findings, usually an opportunistic pathogen (eg, cryptococcosis, mycobacterial granulomas, or molluscum contagiosum).
What are pre-Kaposi sarcoma lesions and anaplastic Kaposi sarcoma?
These are at the two opposite ends of the spectrum of Kaposi sarcoma. Pre-KS lesions are also referred to as an “in situ” form of KS. These pre-KS lesions are characterized by groups of abnormal capillary-like vessels admixed with an inflammatory infiltrate, similar to patch-stage KS lesions. They are associated with lymphangiogenesis arising in the setting of chronic lymphedema. On the other end of the spectrum is anaplastic KS, sometimes referred to as pleomorphic KS. Anaplastic KS is an infiltrative, solid proliferation of spindle cells without vascular spaces, seen mainly in AIDS involving acral sites. This aggressive variant displays a greater degree of cellular and nuclear atypia, high mitotic index (eg, 5 to 20 mitoses per 10 high-power fields), and occasional necrosis.
IHC for Kaposi sarcoma.
Kaposi sarcoma lesional cells stain positively with the endothelial markers factor VIII–related antigen, CD31 (PECAM-1), and CD34. CD34 tends to show stronger expression than CD31 in advanced-stage lesions of KS. KS spindle cells also express several lymphatic specific markers such as D2-40 (which binds to the podoplanin antigen), LYVE-1 (a homologue of the CD44 glycoprotein receptor for hyaluronan), VEGFR-3 (the receptor for vascular endothelial growth factor C), and Prox-1. Bcl-2 also shows positivity in KS, related to the tumor’s mechanisms of resisting apoptosis. The identification and localization of HHV8 within KS lesional cells by using LNA-1 (also called LANA-1) is the most diagnostically helpful immunostaining technique available to differentiate KS from its mimics. LNA-1 immunoreactivity in KS cells appears as stippled nuclear staining. However, HHV8 is not entirely limited to KS and has been detected in some angiosarcomas, hemangiomas, and dermatofibromas. LNA-1 IHC is favored over PCR detection of HHV8 in the evaluation of problematic vascular proliferations because contaminating mononuclear inflammatory cells may also harbor this herpesvirus, especially in HIV-positive patients.
Histologic differential diagnosis for the patch, plaque, and nodular stages of Kaposi sarcoma.
Clinical history, such as HIV infection or status post transplant, may strongly support the diagnosis of KS. The differential diagnosis of patch-stage KS includes targetoid hemosiderotic hemangioma, fibrous histiocytoma, and interstitial granuloma annulare. The differential diagnosis of plaque-stage KS includes tufted angioma, targetoid hemosiderotic hemangioma, microvenular hemangioma, and acroangiodermatitis (“pseudo-Kaposi sarcoma”). The differential diagnosis of nodular KS includes bacillary angiomatosis, other vascular tumors (eg, spindle cell hemangioma and Kaposiform hemangioendothelioma), fibrohistiocytic tumors (eg, cellular, angiomatoid, and atypical variants of fibrous histiocytoma, and dermatofibrosarcoma protuberans), resolving dermal fasciitis, spindle cell melanoma, and several other spindle cell mesenchymal neoplasms (eg, cutaneous leiomyosarcoma).
What are nonmalignant medical conditions associated with reactive eosinophilia?
Allergic reactions (drug reactions, asthma), parasitic infections (strongyloidiasis), schistosomiasis, filariasis, toxocariasis), metabolic abnormalities (adrenal insufficiency), humoral immunodeficiency (hyperimmunoglobulin E syndrome (Job syndrome), Wiskott-Aldrich syndrome, hyperimmunoglobulin M syndrome, immunoglobulin A deficiency), pulmonary eosinophilias (eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), allergic bronchopulmonary aspergillosis, chronic and acute idiopathic eosinophilic pneumonias), autoimmune blistering skin diseases (dermatitis herpetiformis, bullous pemphigoid).
Overview of PML.
Progressive multifocal leukoencephalopathy (PML), also known as progressive multifocal leukoencephalitis, is a rare and usually fatal demyelinating disease characterized by progressive multifocal white matter damage and inflammation, due to the JC virus. It is almost always associated with immunosuppression, including immunosuppressive/biologic therapy for autoimmune diseases, such as natalizumab for multiple sclerosis, and other agents for rheumatoid arthritis or lymphoma. Lytic infection of CNS oligodendrocytes leads to their destruction and progressive demyelination, resulting in multifocal lesions. Although PML previously was relatively rare, it now occurs in 3-5% of HIV+ individuals, and is classified as an AIDS-defining illness. Biopsies show multiple foci of demyelination with enlarged and bizzare astrocytes, which are often multinucleated and have multiple large processes. Oligodendrocytes may have eosinophilic or basophilic nuclear inclusions, due to virions. Lymphocytic infiltration is variable. Necrosis with inflammation resembling an infarct may also be seen. Treatment consists of reversal of the immunosuppression, if possible.
What 2 GI infections can mimic Crohn disease?
Various infectious agents can mimic Crohn disease, the common being infections due to Yersinia and Mycobacterium tuberculosis. Yersinia infections very closely mimic Crohn disease: both diseases can show ileo-colonic involvement, fissuring ulcers, granulomas and transmural inflammation. Similarly granulomatous infection with mycobacteria can closely mimic Crohn disease with granulomas. However, granulomas in Mycobacterial infections are also seen in draining lymph nodes, as opposed to Crohn where they are restricted mostly to the intestine. Transverse ulcers are more characteristic of mycobacterial infection as opposed to longitudinal ulcers and cobblestoning in Crohn disease. Infectious colitis may show diffuse colonic involvement, increased chronic inflammatory cells and neutrophils. In contrast to Crohn disease, neutrophils are often more prominent in the lamina propria compared to the crypts. The architecture is generally preserved.
Histologic appearance of lymphomatoid granulomatosis (LYG).
Morphologically, LYG is angiocentric and may show large zones of necrosis with preservation of viable cells around blood vessels, although necrosis may not be as prevalent in cases of grade 1 LYG. While on initial evaluation the lesion may appear to be a mixture of T- and B- lymphocytes, careful inspection will reveal the atypical morphology of the B-cells. Additionally, LYG is an EBV driven process and the neoplastic B-cells will be positive for EBV latent membrane protein in most cases.
What virus does lymphomatoid granulomatosis have an association with?
EBV. LYG is an EBV driven process and the neoplastic B-cells will be positive for EBV latent membrane protein in most cases.
Benign lymphoepithelial cystic lesions in the salivary gland are seen in association with HIV infection. Describe.
Salivary gland enlargement associated with a significant lymphoid infiltrate is recognized in HIV-positive patients. Because the lymphoid tissue usually exhibits morphologic and immunophenotypic features similar to those seen in florid follicular hyperplasia and the lesions often occur in association with enlarged lymph nodes, benign lymphoepithelial cystic lesions are thought to represent a manifestation of persistent, generalized lymphadenopathy. AKA benign lymphoepithelial lesion, benign lymphocpithelial cyst, cystic lymphoid hyperplasia, and HIV-related salivary gland disease. The lesion most commonly arises in the parotid gland where it occurs in 3-6% of adults and 1-10% of children with HIV. Overall, benign lymphoepithelial cystic lesions account for ~25% of enlarged salivary glands in the HIV positive patient population. The lesions are often cystic, bilateral, multiple, and associated with lymphadenopathy. Morphologically, they are characterized by epithelial-lined cysts, often with squamous metaplasia, follicular hyperplasia, glandular atrophy, and in some cases epimyoepithelial islands. In many patients, treatment with HAART results in smaller lesions or their complete resolution.
The risk of developing lymphoma for patients with HIV-related multicentric Castleman Disease is ~__x higher than it is for the general HIV-positive patient population.
The risk of developing lymphoma for patients with HIV-related multicentric Castleman Disease is ~15x higher than it is for the general HIV-positive patient population. The survival of patients with HIV MCD who develop lymphoma is poor.
The incidence of non-Hodgkin lymphoma in HIV+ individuals is ~__ to __x greater than that of the general population.
The incidence of non-Hodgkin lymphoma in HIV+ individuals is ~70 to 80x greater than that of the general population.
Although not considered an AIDS-defining illness, HIV+ individuals have a __ to __x greater risk of developing cHL than immunocompetent patients.
Although not considered an AIDS-defining illness, HIV+ individuals have a 5 to 15x greater risk of developing cHL than immunocompetent patients. The incidence of HIV cHL has increased with the advent of HAART. Furthermore, the relative risk of developing cHL is higher in patients on HAART than it is in those who are not.
The HIV-related plasmablastic lymphomas characteristically arise in what location?
The HIV-related plasmablastic lymphomas characteristically arise in the oral cavity (60% of cases); however, they can also occur in other mucosal sites, such as the sinonasal cavity and the GI tract, and in nonmucosal sites, such as the skin, soft tissue, and lymph nodes.
What lymphoid proliferations are seen in association with HIV?
Progressive HIV-related lymphadenopathy/HIV-related benign lymphadenopathy. Benign lymphoepithelial cystic lesions. Multicentric Castleman disease. Lymphomas associated with HIV can be subcategorized as those occuring (1) also in immunocompetent patients (most cases), (2) more specifically in HIV+ patients (~5% of cases), and (3) in other immunodeficiency states (<5% of cases). The main entities in (1) are BL (~30% of HIV-related lymphomas), DLBCL (~40%), and cHL (~5-15%). These neoplastic entities account for most of the HIV-related lymphoma, although only the first 2 entities are AIDS-defining diseases. The neoplasms in (2) are highly associated with infection by EBV, KSHV/HHV8, or both. They include: Plasmablastic lymphoma. KSHV+/HHV8+ large B-cell lymphoma associated with MCD. Primary effusion lymphoma/Extracavitary primary effusion lymphoma. In (3), the HIV polymorphic lymphoid proliferations, which resemble the polymorphic poasttransplant-associated lymphoproliferative disorders seen in solid organ transplant recipients, comprise thie category of HIV-related lymphoma/lymphoma-like lymphoproliferative disorders.
For testing blood donors, list the infectious diseases that fall into each of the following 3 categories: Tests are available but may not detect early-stage or window-period infections. Tests are available but not used in all donor centers. No licensed laboratory tests are available for blood donor screening.
Tests are available but may not detect early-stage or window-period infections: Chagas disease. Hepatitis (HBV, HCV). HIV-1,-2. HTLV, types I and II. West Nile Virus. Tests are available but not used in all donor centers: HIV group O. No licensed laboratory tests are available for blood donor screening: Babesiosis. CJD. Variant CJD. Malaria.
Hantavirus pulmonary syndrome. During the HPS prodrome, thrombocytopenia is the only dependable finding. Once pulmonary edema is established, however, there is a highly reproducible pentad of findings:_____.
Hantavirus pulmonary syndrome. During the HPS prodrome, thrombocytopenia is the only dependable finding. Once pulmonary edema is established, however, there is a highly reproducible pentad of findings: thrombocytopenia, left-shifted neutrophilia, neutrophils with lack of significant toxic granulation, increased hemoglobin concentration (hemoconcentration), and >10% of lymphocytes having immunoblastic morphology. Having 4 of these 5 has a high sensitivity and specificity for HPS.
Isolated lymphopenia is uncommon but may be seen in what conditions (6)?
Isolated lymphopenia is uncommon but may be seen in SLE, HIV, SARS, anti-CD20 (rituxan) therapy, steroid therapy, and certain congenital immunodeficiencies (Bruton, SCID, DiGeorge, CVI).
What are some entities that cause a follicular pattern of hyperplasia (reactive follicular hyperplasia) in a lymph node?
Nonspecific reactive follicular hyperplasia (etiology unknown) is the most common scenario. HIV infection produces a profound variety called florid follicular hyperplasia. RA and Sjogren syndrome produce RFH, frequently with interfollicular plasmacytosis. Syphilis also produces a RFH with interfollicular plasmacytosis, but also causes capsular and trabecular thickening (due to chronicity) and capsular infiltration by plasma cells. Castleman disease.
What are some entities that cause an interfollicular pattern of nonneoplastic proliferation in a lymph node?
Viral infections such as infectious mononucleosis, CMV, and postvaccinial lymphadenitis. Hypersensitivity reactions, such as from dilantin. Kimura disease.
What are some entities that cause a sinus pattern of nonneoplastic proliferation in lymph node?
Sinus histiocytosis, a nonspecific reaction to numerous lymph node stimuli. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Lymphangiogram effect. Whipple disease. Hemophagocytic syndrome. Dermatopathic lymphadenitis.
What are some entities that cause a diffuse pattern of nonneoplastic proliferation in lymph node?
The diffuse pattern of nodal expansion, easy to confuse with lymphoma, is produced by several viruses, particularly EBV, but also CMV, HSV, measles, or post-vaccinia lymphadenitis.
The degree of leukoreduction depends on the goal. If meant to prevent febrile reactions, the unit must contain <__ WBCs.
The degree of leukoreduction depends on the goal. If meant to prevent febrile reactions, the unit must contain <5x10^6 WBCs.
What are etiologies of HCC?
Multiple risk factors can contribute to the development of this neoplastic process, such as viral hepatitis infection with HBV or HCV, cirrhosis (independently of cause), exposure to aflatoxin, use of anabolic steroids and tyrosemia.
What are some nonmolecular methods and molecular methods for detecting M. tuberculosis complex (with or without the simultaneous detection of genes conferring drug resistance)?
Nonmolecular methods: Microscopic observation direct susceptibility assay (MODS assay). Light-emitting diode microscopy. MDR-XDRTB Colour Test. Colorimetric assays. Phage amplification assays. Molecular methods: Line probe assays. Automated nucleic acid amplification tests. Loop-mediated isothermal amplification. Oligonucleotide microarray.
What is hairy leukoplakia AKA oral hairy leukoplakia?
An EBV-associated epithelial hyperplasia usually on the lateral tongue in immunocompromised patients, most commonly HIV+ males. The disease correlated with viral load and CD4 counts. Although not an AIDS-defining disease, is a marker of HIV disease progression. Micro: Marked acanthosis and parakeratosis. Epithelial hyperplasia with elongation of rete ridges. Viral cytopathic effect (balloon cells) in spinous layer. Candida can be seen in superficial keratin - coinfection is a common finding in OHL. Very little if any inflammation. No dysplasia. DDx: Frictional keratosis. Hyperplastic candidiasis. Leukoplakia. Lichen planus.
Is oral hairy leukoplakia an AIDS-defining illness?
No. OHL is an EBV-associated epithelial hyperplasia usually on the lateral tongue in immunocompromised patients, most commonly HIV+ males but seen in transplant patients as well. The disease correlated with viral load and CD4 counts. Although not an AIDS-defining disease, is a marker of HIV disease progression.
What is herpangina?
Herpangina is a common viral infection of young children associated with blisters of soft palate or tonsillar pillars. It is caused by viruses belonging to the Enterovirus group (coxsackievirus, poliovirus, echovirus). Coxsackie A16 virus is the most common cause. Transmission is direct contact, usually oral-fecal route.
What virus is the most common cause of herpangina?
Herpangina is a common viral infection of young children associated with blisters of soft palate or tonsillar pillars. It is caused by viruses belonging to the Enterovirus group (coxsackievirus, poliovirus, echovirus). Coxsackie A16 virus is the most common cause, but other coxsackie viruses usually associated include A1 to A6, A8, A10, or A22.
What is hand, foot, and mouth disease?
A common viral illness of infants and children, which causes fever and blister eruptions of mouth and/or skin. Caused by virus belonging to Enterovirus group. Transmission is by direct contact. Virus is found in secretions, including saliva, nose and throat secretions, blister fluid, and stools.
What is Heck disease?
AKA focal epithelial hyperplasia AKA multifocal epithelial hyperplasia. A benign, virus-induced epithelial proliferation of oral mucosa associated with HPV types 13 and 32. Majority of cases are in children. Micro: Prominent acanthosis and elongated broad rete ridges (since the thickened epithelium extends upward, elongated rete are at same depth as adjacent normal rete ridges). May see papillary surface. Mitosoid cells (represents ballooning and nuclear degeneration; represents an altered nucleus resembling a mitosis in an otherwise normal stratified squamous epithelium; can be seen throughout epithelium); do not misinterpret mitosoid cells as atypia. Koilocytic change in superficial keratinocytes can be seen. No dyskeratosis and/or atypia. DDx: Papilloma. Condyloma acuminatum. Oral verruca vulgaris.
What HPV types cause Heck disease (focal epithelial hyperplasia/multifocal epithelial hyperplasia)?
HPV types 13 and 32.
What are the definitions of squamous papilloma, verrucae vulgaris, and condyloma accuminatum?
SP: Benign proliferation of squamous epithelium in exophytic pattern with branching fibrovascular tissue cores exhibiting papillary pattern causally related to HPV infection (subtypes 6 and 11 detected in ~50% of cases, rarely HPV 16 detected). VV (AKA common wart or oral wart): Benign HPV-induced (subtypes 2, 4, 6, 40, or 57 detected in 100% of cases) proliferation of squamous epithelium, usually on skin, but also in oral cavity. CA (AKA veneral wart): HPV-related (subtypes 2, 6, 11, 53, or 54 in oral area, rarely 16, 18, or 31 (usually anogenital)) proliferation of squamous epithelium of genitalia, perianal region, oral cavity, or larynx.
What is oropharyngeal carcinoma?
Basically is a squamous cell carcinoma of oropharynx, the sites including soft palate, tonsils, uvula, base of tongue, and oropharyngeal wall comprising Waldeyer ring. Is also called oropharyngeal squamous cell carcinoma (OPSCC). What is typically called oral squamous cell carcinoma involves the sites of tongue (lateral and ventral), floor of mouth, lip, retromolar trigone, gingiva, buccal mucosa, and palate. HPV+ OPSCC is nonkeratinizing, while HPV- OPSCC is keratinizing. Other subtypes include: Hybrid-type OPSCC, which has features of both nonkeratinizing OPSCC and keratinizing SCC; is HPV+ most of the time. Lymphoepithelial-like OPSCC, which is similar in histology to EBV-related nasopharyngeal carcinoma; is HPV+. Papillary OPSCC, which is an uncommon variant; most are HPV+.
What are hematological indicators of poor prognosis in severe malaria?
Malaria is the single most important disease hazard from travel to developing countries. Worldwide, there are over 200 million annual cases with over 600,000 annual deaths. Hematological indicators of poor prognosis in severe malaria include a platelet count < 50 x 10E9/L, prolonged PT >3 seconds, prolonged APTT, fibrinogen < 200mg/dl, hyperparasitemia > 100,00/uL (high mortality if >500,000/uL), > 20% parasites and > 5% neutrophils containing visible malarial pigment. Early recognition and prompt management are important.
HIV salivary gland disease.
AKA AIDS-related parotid cyst. HIV-SGD includes HIV-infected individuals with xerostomia, enlargement of one or more major salivary glands, or both. Mostly adult men 20-60 yo. M:F = 9:1. 98% in parotid, 2% in submandibular gland. Bilateral involvement in 60%. Early phases include florid follicular hyperplasia, attenuated to absent mantle lymphocytes, disruption of germinal centers (follicle lysis). MGCs localized to inter-/intrafollicular and periepithelial areas commonly seen. Multiple squamous epithelial-lined cysts and epimyoepithelial islands present.
How can benign lymphoepithelial cyst be differentiated from HIV-associated salivary gland disease?
HIV-SGD is typically multiple, possibly bilateral, and also contain lymphoepithelial islands. Their germinal centers are larger and more irregular, with interfollicular tissue containing numerous plasma cells, neutrophils, histiocytes, and large, irregular mononuclear or multinuclear cells.
What is the Laboratory Response Network?
The LRN is a laboratory testing and referral system formed as an outgrowth of the CDC’s Health Alert Network. Its purpose is to prepare for and provide a coordinated, rapid response to bioterrorism and other public health emergencies. The LRN consists of four types of laboratories, designated Levels A, B, C, and D.
What are the types of laboratories in the Laboratory Response Network?
The LRN consists of four types of laboratories, designated Levels A, B, C, and D. Level A labs must always operate in compliance with accepted BSL-2 requirements. When handling any potential pathogen, all Level A labs should utilize BSL-3 practices for all culture manipulations that might produce aerosols. Level B labs operate in compliance with all BSL-2 requirements and always practice BSL-3 safety procedures. Level C labs operate in compliance with all BSL-3 safety requirements and are certified as BSL-3 facilities. Their staff is specially trained to handle highly pathogenic and potentially lethal agents.
What are biosafety levels?
A biosafety level is the level of the biocontainment precautions required to isolate dangerous biological agents in an enclosed facility. The levels of containment range from the lowest biosafety level 1 (BSL-1) to the highest at level 4 (BSL-4). Higher numbers indicate a greater risk to the external environment. In the United States, the CDC has specified these levels.
Biosafety Level 1.
This level is suitable for work involving well-characterized agents not known to consistently cause disease in healthy adult humans, and of minimal potential hazard to laboratory personnel and the environment. It includes several kinds of bacteria and viruses including canine hepatitis, non-pathogenic E. coli, as well as some cell cultures and non-infectious bacteria. At this level, precautions against the biohazardous materials in question are minimal and most likely involve gloves and some sort of facial protection. The laboratory is not necessarily separated from the general traffic patterns in the building. Work is generally conducted on open bench tops using standard microbiological practices. Usually, contaminated materials are left in open (but separately indicated) waste receptacles. Decontamination procedures for this level are similar in most respects to modern precautions against everyday microorganisms (i.e., washing one’s hands with anti-bacterial soap, washing all exposed surfaces of the lab with disinfectants, etc.). In a lab environment all materials used for cell and/or bacteria cultures are decontaminated via autoclave. Laboratory personnel have specific training in the procedures conducted in the laboratory and are supervised by a scientist with general training in micro or a related science.
Biosafety Level 2.
This level is similar to Biosafety Level 1 and is suitable for work involving agents of moderate potential hazard to personnel and the environment. It includes various bacteria and viruses that cause only mild disease to humans, or are difficult to contract via aerosol in a lab setting, such as C. difficile, most Chlamydiae, hepatitis A, B, and C, orthopoxviruses (other than smallpox), influenza A, Lyme disease, Salmonella, mumps, measles, scrapie, MRSA, and VRSA. BSL-2 differs from BSL-1 in that: (1) laboratory personnel have specific training in handling pathogenic agents and are directed by scientists with advanced training, (2) access to the laboratory is limited when work is being conducted, (3) extreme precautions are taken with contaminated sharp items; and (4) certain procedures in which infectious aerosols or splashes may be created are conducted in biological safety cabinets or other physical containment equipment.
Biosafety Level 3.
This level is applicable to clinical, diagnostic, teaching, research, or production facilities in which work is done with indigenous or exotic agents which may cause serious or potentially lethal disease after inhalation. It includes various bacteria, parasites and viruses that can cause severe to fatal disease in humans but for which treatments exist, such as F. tularensis, L. donovani, M. tuberculosis, C. psittaci, West Nile virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, SARS coronavirus, C. burnetii, Rift Valley fever virus, R. rickettsii, several species of Brucella and yellow fever virus. Lab personnel have specific training in handling pathogenic and potentially lethal agents, and are supervised by competent scientists who are experienced in working with these agents. This is considered a neutral or warm zone. All procedures involving the manipulation of infectious materials are conducted within biological safety cabinets, specially designed hoods, or other physical containment devices, or by personnel wearing appropriate personal protective clothing and equipment. The laboratory has special engineering and design features.
Biosafety Level 4.
This level is required for work with dangerous and exotic agents that pose a high individual risk of aerosol-transmitted laboratory infections, agents which cause severe to fatal disease in humans for which vaccines or other treatments are not available, such as Bolivian and Argentine hemorrhagic fevers, Marburg virus, Ebola virus, Lassa virus, Crimean-Congo hemorrhagic fever, and various other hemorrhagic diseases. This level is also used for work with agents such as Smallpox that are considered dangerous enough to require the additional safety measures, regardless of vaccination availability. When dealing with biological hazards at this level the use of a positive pressure personnel suit, with a segregated air supply, is mandatory. The entrance and exit of a level four biolab will contain multiple showers, a vacuum room, a UV light room, and other safety precautions designed to destroy all traces of the biohazard. Multiple airlocks are employed and are electronically secured to prevent both doors opening at the same time. All air and water service going to and coming from a biosafety level 4 (or P4) lab will undergo similar decontamination procedures to eliminate the possibility of an accidental release. The facility is either in a separate building or in a controlled area within a building, which is completely isolated from all other areas of the building. A specific facility operations manual is prepared or adopted. Building protocols for preventing contamination often use negatively pressurized facilities, which, even if compromised, would severely inhibit an outbreak of aerosol pathogens.
The CDC and other governmental agencies list biological agents/diseases in three categories (A, B, and C) according to priority of risk and ease of ability to disseminate to the population. Give the characteristics of category A agents, and list out the agents.
Category A agents are the highest priority of agents that pose a national security risk. They: can be easily disseminated or transmitted from person to person; result in high mortality rates and have the potential for major public health impact; might cause public panic and social disruption; and require special action for public health preparedness. They include: anthrax (Bacillus anthracis), botulism (Clostridium botulinum), plague (Yersinia pestis), smallpox (variola major), tularemia (Francisella tularensis), and viral hemorrhagic fevers - filoviruses (i.e., Ebola, Marburg) and arenaviruses (i.e., Lassa, Machupo).
The CDC and other governmental agencies list biological agents/diseases in three categories (A, B, and C) according to priority of risk and ease of ability to disseminate to the population. Give the characteristics of category B agents, and list out the agents.
Second highest priority agents include those that: are moderately easy to disseminate; result in moderate morbidity rates and low mortality rates; and require specific enhancements of CDC’s diagnostic capacity and enhanced disease surveillance. They include: Brucellosis (Brucella species), Epsilon toxin of Clostridium perfringens, Food safety threats (e.g., Salmonella species, Escherichia coli O157:H7, Shigella), Glanders (Burkholderia mallei), Melioidosis (Burkholderia pseudomallei), Psittacosis (Chlamydia psittaci), Q fever (Coxiella burnetii), Ricin toxin from Ricinus communis (castor beans), Staphylococcal enterotoxin B, Typhus fever (Rickettsia prowazekii), Viral encephalitis (alphaviruses [e.g., Venezuelan equine encephalitis, eastern equine encephalitis, western equine encephalitis]), Water safety threats (e.g., Vibrio cholerae, Cryptosporidium parvum).
The CDC and other governmental agencies list biological agents/diseases in three categories (A, B, and C) according to priority of risk and ease of ability to disseminate to the population. Give the characteristics of category B agents, and list out the agents.
Third highest priority agents include emerging pathogens that could be engineered for mass dissemination in the future because of: availability; ease of production and dissemination; and potential for high morbidity and mortality rates and major health impact. They include: emerging infectious diseases such as Nipah virus and hantavirus; other emerging pathogens that could be engineered for mass destruction.
B. anthracis is present in soil throughout the world; in the United States, it is found mostly ___.
B. anthracis is present in soil throughout the world; in the United States, it is found mostly along old cattle trails in Texas, Louisiana, Mississippi, Arkansas, New Mexico, Oklahoma, and some Midwestern states. However, anthrax is rare in the United States because it is controlled in animal populations by vaccination programs.
About 90% of all human anthrax cases reportedly occur in people in what specific occupation?
About 90% of all human anthrax cases reportedly occur in millworkers handling imported goat hair.
How was Bacillus anthracis named?
The word anthracis comes from the Greek word meaning “coal,” and the bacterium was so named because the microbe can cause a black scab (eschar) to form on the skin of cutaneous anthrax victims. For the same reason, it is sometimes called the “black carbuncle.”
What is “weapons grade” anthrax?
Anthrax is the single greatest biowarfare threat because it is easy to cultivate spores, although production of a weaponized spore is not so simple. The media sometimes refer to “weapons grade” anthrax versus “nonweapons grade.” Criteria for weapons grade include small spore size, usually 1–3 microns; lack of clumping (usually accomplished by adding a polymer that prevents the natural tendency of spores to clump); the quantity of spores present; and an effective delivery system.
In nature, approximately __% of human cases of anthrax are cutaneous infections, as opposed to inhalation anthrax or GI anthrax.
In nature, approximately 95% of human cases of anthrax are cutaneous infections, as opposed to inhalation anthrax or GI anthrax.
What are the 4 virulence factors of Bacillus anthracis?
Anthrax spores can survive inside macrophages, eventually vegetating and growing to such numbers that they cause the cells to burst and release bacilli into the bloodstream. These bacteria produce four virulence factors; three are toxins that cause systemic symptoms: protective antigen toxin, the lethal factor, and the edema factor. Last, anthrax produces a capsule that protects it from destruction by the body’s leukocytes. Once systemic symptoms occur, antibiotics are useless because they have no effect on the circulating toxins.
Once Bacillus anthracis infection causes systemic symptoms, why are antibiotics useless?
These bacteria produce four virulence factors; three are toxins that cause systemic symptoms: protective antigen toxin, the lethal factor, and the edema factor (the fourth is a capsule that protects it from destruction by the body’s leukocytes). Once systemic symptoms occur, antibiotics are useless because they have no effect on the circulating toxins.
How is inhalational anthrax a biphasic disease?
It has initial and acute phases. The initial phase is characterized by mild flu-like symptoms (e.g., malaise, fatigue, low-grade fever) followed by a period of apparent wellness for about a day. This is immediately followed by the acute phase, which eventually leads to more serious symptoms (e.g., acute respiratory distress). The incubation period can vary from 1–5 days, depending on the number of spores inhaled, but can be as long as 60 days. Shock and death usually occur 24–36 hours after the onset of respiratory distress. The fatality rate of inhalation anthrax approaches 90%, even with antibiotic therapy.
Is anthrax spread via person-to-person transmission?
No.
What is the incubation period for cutaneous anthrax?
This form of anthrax occurs after spores are introduced beneath the skin by inoculation or contamination of a preexisting lesion or break in the skin. The incubation period is 2–7 days (rarely after 1 day) but more often lasts between 2 and 5 days. Lesions begin as small, painless pimples on exposed skin and progress to vesicles and eventually an ulceration that develops a black scab (eschar) at the center (within 2–6 days).
What are fatality rates for the 3 forms of anthrax?
The fatality rate of inhalation anthrax approaches 90%, even with antibiotic therapy. Untreated cutaneous anthrax can have a fatality rate of up to 20%, but fatalities are rare (1%) with proper antibiotic treatment. The fatality rate for GI anthrax is 25%–60%.
How does GI anthrax occur?
This form of anthrax occurs by ingesting contaminated meat, in particular raw or undercooked, from infected animals. It has also been reported in association with animal-hide drums. The incubation period is 2–7 days.
What are the 2 forms of GI anthrax?
Two types of GI anthrax are characterized by different symptoms: intestinal (e.g., nausea, vomiting, diarrhea) and oropharyngeal (e.g., neck swelling, difficulty swallowing). Shock and toxemia can characterize both forms of the disease, especially in the terminal stages.
What is the role of the level A laboratory in identification of Bacillus anthracis?
Presumptively identify based on criteria below (direct smears, culture smears, colonies on sheep blood agar, and other criteria), and then submit culture to a Level B or C laboratory for final identification. Direct smears: Samples such as blood, CSF, and skin (eschar) show encapsulated gram-positive rods, single or in chains. Generally, spores not seen. Culture smears: Large gram-positive bacilli (1–1.5 by 3–5 µm), which may be gram-variable after 72 hours; spores can be found in culture, especially under non-CO2 atmosphere but are nonswollen and are terminal or subterminal. Colonies on sheep bloor agar plates: Rapidly growing 2–5 mm (overnight at 35° C), nonhemolytic, nonpigmented, dry “ground-glass” surface colonies with irregular edges having comma-shaped projections (Medusa head). The colony has a sticky (tenacious) consistency when teased with a loop. Other criteria: Nonmotile, catalase-positive, urease-negative, nitrate-positive, encapsulated bacillus that can be lysed by gamma phage (gamma phage typing is usually performed by Level B or C laboratory).
For anthrax (Bacillus anthracis), how is the diagnosis made, what specimens should be collected/what lab tests should be performed, and what is treatment/prophylaxis/vaccination?
Diagnosis: Clinical evaluation and laboratory findings. Tests and specimens: Culture: Blood, CSF, wounds (definitive). Nasal culture: Determines extent of spore spread in population. Immunohistochemical (IHC): Tissue. PCR: Can confirm diagnosis if culture is negative. Serology: ELISA, IFA. Treatment: Antibiotics, including penicillin, quinolones, tetracycline. Treat inhalation anthrax for 60 days. Can combine antibiotics (30 days) and vaccine (3 doses at 0, 14, and 28 days). Full vaccination regimen is 6 doses at 0, 2, and 4 weeks and 6, 12, and 18 months followed by yearly boosters.
For plague (Yersinia pestis), how is the diagnosis made, what specimens should be collected/what lab tests should be performed, and what is treatment/prophylaxis/vaccination?
Diagnosis: Clinical evaluation and laboratory findings. Tests and specimens: Culture: Sputum, blood, lymph. Direct FA: Respiratory secretions. Serology: F1–V antigen (fusion protein) assay. Treatment: Antibiotics, including tetracycline; quinolones, streptomycin, gentamicin, and chloramphenicol for 10–14 days. Prophylaxis: Medication for 7 days. Formalin-killed vaccine given 0, 1, and 4–7 months. Boosters every 1–2 years.
For Brucellosis (Brucella species), how is the diagnosis made, what specimens should be collected/what lab tests should be performed, and what is treatment/prophylaxis/vaccination?
Diagnosis: Difficult with many rule-outs; laboratory required. Tests and specimens: Culture: Nasal, sputum, respiratory specimens (can also use PCR); blood culture is definitive test. Serology: IFA, ELISA, and microagglutination (gold standard) to detect antibodies. Treatment: Combination antibiotics (6 weeks): Doxycycline and rifampin or quinolone and rifampin. Prophylaxis requires 3 weeks. Numerous vaccines (both killed or live attenuated) available with no proven success.
For Tularemia (Francisella tularensis), how is the diagnosis made, what specimens should be collected/what lab tests should be performed, and what is treatment/prophylaxis/vaccination?
Diagnosis: Difficult with many rule-outs; laboratory required (key symptom: pneumonia with nonproductive cough). Tests and specimens: General laboratory tests not helpful. Culture: Bacterium does not grow on ordinary media, needs cysteine blood or chocolate agar. Capsular AG detection or PCR: Whole unclotted blood. Direct FA and PCR: Nasal, induced respiratory specimens. IHC: Tissue sometimes helpful. Serology: ELISA AB. Treatment: Antibiotics like gentamicin, streptomycin, ciprofloxacin. Prophylaxis: Doxycycline. Vaccine: Live attenuated available.
For Botulism (Clostridium botulinum), how is the diagnosis made, what specimens should be collected/what lab tests should be performed, and what is treatment/prophylaxis/vaccination?
Diagnosis: Clinical evaluation; routine laboratory tests are of no value; toxin assay may be useful if toxin present in serum. Tests and specimens: PCR and toxin assay: Use nasal induced respiratory secretions and blood. Treatment: Supportive treatment: Antitoxin can be administered up to 24 hours after exposure: two types, trivalent and pentavalent. Also available is a pentavalent toxoid vaccine.
For Smallpox (variola major), how is the diagnosis made, what specimens should be collected/what lab tests should be performed, and what is treatment/prophylaxis/vaccination?
Diagnosis: Clinical findings (exanthems). Tests and specimens: Cell or chick embryo culture: Skin lesions ideal; nasal swabs, respiratory secretions, serum specimens can also be cultured. Electron microscopy: Identifies virus. PCR: Use same specimens as earlier. Agar gel precipitation: Skin lesions. Serology: Tests are available. Treatment: VIG must be used in conjunction with vaccinia vaccine if exposure occurs beyond a 3-day time frame. Within 3 days, only vaccinia vaccine need be given by scarification. Cidofovir offers promise.
For Venezuelan equine encephalitis, how is the diagnosis made, what specimens should be collected/what lab tests should be performed, and what is treatment/prophylaxis/vaccination?
Diagnosis: Difficult with many rule-outs; laboratory required. Tests and specimens: PCR or culture in cells/suckling mice: Nasal, induced respiratory secretions and serum. Serology: ELISA, IFA, and hemagglutination inhibition; detect AB. Treatment: Some drugs show promise. At present, no specific therapy. Treatment geared toward relieving symptoms. Some vaccines show promise (i.e., TC-84).
For viral hemorrhagic fevers, how is the diagnosis made, what specimens should be collected/what lab tests should be performed, and what is treatment/prophylaxis/vaccination?
Diagnosis: Clinical evaluation; key finding is vascular involvement (i.e., petechiae, bleeding, postural hypotension, edema, etc.). Tests and specimens: General: Leukopenia, thrombocytopenia; elevated AST. Serology: ELISA, IFA, and PCR; detect different VHFs. Treatment: Management of hypotension and fluid loss. Aggressive supportive care needed. Ribavirin and immune globulin therapy show some promise. Several vaccines under development.
What is the role of the level A laboratory in identification of Yersinia pestis?
Presumptively identify based on criteria below (direct smears, culture smears, colonies on sheep blood agar, and other criteria), and then submit culture to a Level B or C laboratory for final identification. Direct smears: More likely to see bipolar staining (“safety pin”) from clinical specimens (blood, sputum, aspirates, etc.) than from cultures. Bipolarity is better seen using Wayson or Wright-Giemsa stain. Beware that bipolar staining is not always observed and is not unique to Y. pestis. Culture smears: Plump gram-negative rods (1–2 by 0.5 µm), single or in short chains. Colonies on sheep blood agar: Grow at 35° C (faster at room temperature) as gray-white, nonhemolytic, translucent, pinpoint colonies at 24 hours, but by 48 hours, colonies are 1–2 mm in diameter, becoming yellowish with age. Growth occurs with or without carbon dioxide. Colonies can appear as “fried egg” or with “hammered copper” shiny surface. On MacConkey, grow as pinpoint non–lactose-fermenting colonies after 24 hours; slightly larger at 48 hours. Other criteria: The bacterium is nonmotile at 35° C to 37° C and at room temperature (Y. pestis is the only Yersinia that is nonmotile at room temperature). It is oxidase and urease negative and catalase positive; growth in broth is flocculent and is described as “stalactite”; clumps at side and bottom of tube.
Can pneumonic plague be transmitted person-to-person?
Yes. Pneumonic plague can be transmitted via large aerosol droplets from a coughing patient. It can be transmitted by cats too!
Yersinia pestis is transmitted by ___.
A rat flea (Xenopsylla cheopis, the oriental flea, or Pulex irritans, the human flea).
Yersinia pestis can be killed by (type of cell), but they can survive in (type of cell).
Yersinia pestis can be killed by polymorphonuclear cells, but they can survive in monocytes, where they produce a capsule to resist phagocytosis. These bacteria can then rapidly reach the lymph system and bloodstream and be disseminated to all organs, causing hemorrhage and necrosis.
A (very low/very high) number of organisms are necessary for infection by Yersinia pestis.
A very low number; fewer than 100 organisms are necessary to cause human infection.
Is Yersinia pestis susceptible to heat/light?
The bacterium is killed after heat exposure (15 minutes at 72° C/160° F) and within several hours of exposure to sunlight.
What are the 3 clinical forms of plague?
Bubonic, pneumonic, and septicemic.
The mortality rate of untreated pneumonic plague is ___%, and that of untreated bubonic plague is ~__%.
The mortality rate of untreated pneumonic plague is 100%, and that of untreated bubonic plague is about 50%.
What are the incubation periods for bubonic plague and pneumonic plague?
2-10 days for bubonic plague, 1-3 days for pneumonic plague.
How do pneumonic plague patients transmit infection?
Pneumonic plague patients transmit infection through large particle droplets (greater than 5 microns) generated by coughing, talking, or sneezing. A simple surgical-type mask can protect workers or family members. “Droplet Precautions” should be maintained for 3 complete days of antibiotic therapy, after which a person is no longer contagious. Because “droplets” occur only within 3–5 feet of a patient, central air conditioning systems do not need to be fitted with HEPA filters (i.e., they do not need to provide bacteria- and particle-free air).
What is the role of the level A laboratory in identification of Brucella species?
Presumptively identify based on criteria below (direct smears, culture smears, colonies on sheep blood and chocolate agars, and other criteria) and then submit culture to a Level B or C laboratory for final identification and/or confirmation, although most Level A laboratories are able to completely identify Brucella. Direct smears: Blood and/or bone marrow most often submitted. Brucella appears as faintly staining, small gram-negative coccobacilli (0.5–0.7 by 0.6–1.5 µm), mostly seen as single cells appearing like “fine sand.” Culture smears: Similar to direct smears. Colonies on SBA and CA: Usually not visible or are pinpoint at 24 hours; at 48 hours, colonies are tiny, nonpigmented, and smooth with an entire edge, and are nonhemolytic on SBA. Growth of some strains is enhanced by carbon dioxide tension. Some strains grow on MacConkey; Thayer-Martin can be used as a selective medium. Blood cultures are held for 21 days for suspect cases. Other criteria: These coccobacilli are catalase, urease, and oxidase positive (B. canis is variable). They are nonmotile and do not require X and V factors. Brucellosis is one of the most commonly reported laboratory-acquired infections. Automated systems are not useful, nor are they recommended for identification. Remember that sniffing culture plates of Brucella can result in infection.
Brucellosis is a systemic zoonotic disease caused by Brucella ___, B. ___, B. ___, and B. ___.
Brucellosis is a systemic zoonotic disease caused by Brucella melitensis, B. suis, B. abortus, and B. canis. These bacteria ordinarily cause disease in domestic animals, such as goats, sheep, and camels (B. melitensis); cattle (B. abortus); and pigs (B. suis). The primary pathogen of dogs, B. canis rarely causes disease in humans.
Other names for Brucellosis include ___.
Human disease is called undulant fever, Malta fever, Bang’s disease, Gibraltar fever, and Mediterranean fever and occurs worldwide.
How is Brucellosis transmitted?
Natural infection in humans occurs when bacteria are inhaled as aerosols, ingested in raw unpasteurized infected milk or meat, or introduced into abrasions in skin or through contact with conjunctival surfaces.
In developed countries, human infection with Brucella is associated with what 2 industries?
In developed countries, human infection is associated with the meat packing and dairy industries.
Brucella infections are also called “undulant fever.” How do they produce an undulating pattern of fevers?
Brucellae are intracellular bacteria; they are able to survive phagocytosis and thus can be carried from lymph tissue to blood and deposited in numerous organs. Inside the phagocytes, the bacteria grow, and eventually their host cells are killed, and a new crop of bacteria is released. The “undulant” fever pattern observed with this disease corresponds to the release of bacteria into the blood, thereby causing fever. As these bacteria are eliminated, the fever subsides, only to recur when another crop of bacteria is released. Relapses are common.
What are the two morphologically different colony types of Brucella species?
Brucella species have two morphologically different colony types: smooth and rough. The smooth form is more pathogenic because of the presence of a capsule that protects the bacterium from phagocytosis and destruction.
Brucellosis is a systemic zoonotic disease caused by Brucella melitensis, B. suis, B. abortus, and B. canis. Which two are the most virulent?
B. melitensis and B. suis are more virulent than the other two species and have better intracellular survival.
Brucellosis is a systemic zoonotic disease caused by Brucella melitensis, B. suis, B. abortus, and B. canis. What are the mortality rates for each?
Mortality rate is about 6% for B. melitensis but 1% for the other species.
What is the incubation period for Brucellosis?
The incubation period can be 1–8 weeks but is usually 3–4 weeks.
What is the clinical presentation of Brucellosis?
Onset is insidious, with malaise, fever, chills, sweats, headache, fatigue, myalgias, and arthralgias. Fever usually rises in the afternoon; it falls during the night and is accompanied by drenching sweat. Swollen lymph, spleen, and liver may also be present. The undulant fever can occur over weeks, months, or even years. Yet, there are many days when a patient has no fever and feels relatively well, only to experience another cycle of waxing and waning fever. Patients are often diagnosed with a fever of unknown origin. Cough occurs in about 20% of cases, but the radiograph appears normal. Gastrointestinal symptoms occur in up to 70% of adult cases, although less frequently in children.
Most deaths due to Brucellosis are associated with ___ or ___.
Most deaths are associated with endocarditis or meningitis.
Can Brucellosis be transmitted person-to-person?
Brucellosis cannot be transmitted person-to-person, so that patient isolation is not required. However, contact precautions are indicated if a draining lesion is present. Brucellosis is contracted through eye contact (i.e., rubbing or touching your eyes), so hand washing with germicidal soap or alcohol-based hand sanitizers is an important protective strategy.
What is the role of the level A laboratory in identification of Francisella tularensis?
Presumptively identify based on criteria below (direct smear; culture smear; colonies on sheep blood, chocolate, and blood cysteine agars; and other criteria) and then submit culture to a Level B or C laboratory for final identification. Direct smear: Gram stain of blood, biopsy material, scrapings, or aspirates may be difficult to interpret because bacteria are tiny, pleomorphic, poorly staining gram-negative coccobacilli seen mostly as single cells. Culture smear: Very tiny (0.2–0.5 by 0.7–1.0 µm), poorly staining, pleomorphic, gram-negative coccobacilli. They are smaller than Haemophilus influenzae and Brucella spp. Their minuscule size should raise awareness. Colonies on sheep blood, chocolate, and blood cysteine agars: Grow poorly and slowly on SBA as 1–2 mm gray-white, nonhemolytic colonies after 48–72 hours. On CA and BCA, colonies are slightly larger, 1–3 mm, gray-white to bluish-gray with an entire edge and smooth flat surface. Colonies do not subculture well to SBA (viability is usually lost). Subcultures should be made onto CA, BCA, or Thayer-Martin agar. Carbon dioxide is not required for growth. No growth occurs on MacConkey or eosin methylene blue agar. Other criteria: F. tularensis is nonmotile and oxidase and urease negative; catalase can be weakly positive or negative. X and V factors are not required. Slow growth in thioglycollate broth with a dense band near top, which eventually diffuses downward with time.
Francisella tularensis. Gram positive or negative? Shape? Motile or nonmotile? Spore-forming or non-spore-forming?
The causative agent of tularemia (also known as “rabbit fever”) is Francisella tularensis. These bacteria are gram-negative bacilli that are nonmotile and have no spore form.
How is tularemia (Francisella tularensis) acquired?
Humans acquire this zoonotic disease through contact with animals, usually through the inoculation of skin or their mucous membranes with blood or tissue fluids of infected animals or bites from infected ticks, mosquitoes, or flies. A less common method of acquiring infection is through inhalation of contaminated dusts or ingestion of contaminated foods or water.
Francisella tularensis. Low/moderate/high infectivity?
Because the bacterium is highly contagious, as few as 25 inhaled organisms or as few as 10 organisms administered subcutaneously can cause infection.
Does Francisella tularensis produce a capsule? Can it survive intracellularly?
F. tularensis produces a capsule that allows the organism to avoid immediate destruction by the body’s phagocytes. It can survive as an intracellular parasite within cells of the lymph system.
What are the 6 major forms/syndromes of infection with F. tularensis?
Ulceroglandular tularemia (70%–85% of cases) typically presents with a skin ulcer, usually as the result of a tick bite, and swollen lymph nodes, fever, chills, headache, sweating, and coughing. Glandular tularemia (5%–12% of cases) is characterized by fever and swollen lymph nodes but no obvious skin lesion. Typhoidal tularemia (7%–14% cases) presents with acute onset of fever, chills, headache, vomiting, and diarrhea. Usually no skin lesions or swollen lymph nodes are present, but the condition is associated with primary or secondary pneumonia. Oculoglandular tularemia (1%–2% cases) presents with severe conjunctivitis and swollen lymph nodes, usually as the result of self-inoculating the organism into the conjunctivae. Oropharyngeal tularemia occurs in patients who have a primary lesion in the oropharynx. Patients present with severe headache and bilateral tonsillitis or severe streptococcal-type sore throat. Persistent swollen lymph nodes in the neck appear after 1–2 weeks. Pneumonic tularemia (8%–13% cases) is primarily a complication of the other forms, especially typhoidal tularemia. It is also acquired by inhaling of infectious aerosols or as a result of blood-borne dissemination. Lymph nodes in the lungs are enlarged. Sometimes, the pneumonia is not evident.
What is the most common type/syndrome of tularemia?
Ulceroglandular tularemia (70%–85% of cases) typically presents with a skin ulcer, usually as the result of a tick bite, and swollen lymph nodes, fever, chills, headache, sweating, and coughing.
Which form/syndrome of tularemia has the highest mortality rate?
Typhoidal tularemia (7%–14% cases) presents with acute onset of fever, chills, headache, vomiting, and diarrhea. Usually no skin lesions or swollen lymph nodes are present, but the condition is associated with primary or secondary pneumonia. This form has the highest mortality rate and is the most likely bioterror form.
What is the role of the Level A laboratory in identification of botulinum toxin, staphylococcal toxins, mycotoxin, saxitoxin, ricin, etc.?
Submit specimens immediately to public health laboratory for evaluation and referral, even if criminal activity is not suspected. Level A laboratories should not manipulate specimens, culture, identify, or perform toxin assays. Level A laboratory responsibility is limited to advising the medical staff on specimen selection, packing, shipping, and notifying the recipient laboratory about specimens from a suspected case. For suspect food samples, 25–50 g of food should be submitted in original containers that have been placed in a leakproof sealed system and transported at 4 C. If aerosolized release is suspected, collect nasal swabs for toxin testing and/or polymerase chain reaction analysis and transported at room temperature. For stool or enema fluid, collect 25–50 g into sterile leakproof containers and transport at 4 C. Collect approximately 10 mL of serum for serologic assays and transport at 4 C. Collect environmental and/or other samples on swabs and transport at 4 C.
Clostridia produce protein toxins, the most powerful of which is the botulinum toxin. What are the 7 C. botulinum toxins? Which ones cause human illness?
Seven C. botulinum toxins are known: A, B, C, D, E, F, and G. Human illness is caused by four of the seven toxins: types A, B, E, and F. The toxins bind to synaptic vesicles of cholinergic nerves, preventing release of acetylcholinesterase at peripheral nerve endings (including neuromuscular junctions).
What are the 4 forms of botulism?
The classic type is food-borne botulism, which typically occurs in adults and is caused by ingestion of toxins present in contaminated food. C. botulinum grows in food and produces its toxin. The usual foods involved are canned alkaline foods that are eaten without cooking, and smoked and vacuum-packed foods. Under anaerobic conditions, C. botulinum spores grow into vegetative forms that produce toxin. Wound botulism, the rarest form, occurs when bacteria gain access to a wound site and then produce toxins in vivo. Infant botulism, the most common type, occurs when a child consumes food contaminated with C. botulinum rather than consuming pre-formed toxins. Toxin is produced in the infant’s gut, de novo, and poisons from within. Some botulism patients do not have an obvious food or wound source; they fall into the “classification undetermined” group.
What are the most common and least common forms/types of botulism?
Most common - infant botulism. Least common - wound botulism.
What is the clinical presentation of botulism?
Symptoms usually begin 18–24 hours after ingestion or inhalation of toxin, although this may take several days. Initial symptoms include double vision, lack of coordination of eye muscles, inability to swallow, speech difficulty, generalized weakness, and dizziness. These are followed by descending progressive weakness of the extremities and weakness of the respiratory muscles. No fever is present, and the patient may be totally alert and oriented. Neurologic examination shows flaccid muscle weakness of the tongue, larynx, respiratory muscles, and extremities. A patient remains fully conscious until shortly before death from respiratory paralysis or cardiac arrest.
Do patients who recover from botulinum toxin exposure develop antitoxin in the blood?
No. Suppression of antibody production is probably caused by the toxins, in much the same way that toxic shock syndrome toxin-1 produced by Staphylococcus aureus prevents antibody production.
Is botulinum toxin more toxic and lethal when delivered by inhalation or food-bourne?
Food-bourne.
Does botulinum toxin permeate the skin?
No.
What is the role of the Level A laboratory in identification of smallpox?
Smallpox is highest-level emergency; submit specimens immediately to public health laboratory. Virus is highly infectious; avoid manipulation; if necessary use Biological Safety Level-3 practices. Responsibility of Level A laboratories is limited to advising medical staff on specimen selection, packing and shipping sample, and communicating with reference laboratory. Level A laboratories should not culture, sample, or perform assays on specimens suspected of containing the virus. Clinical diagnosis is confirmed by Level D laboratory techniques. For biopsies, aseptically place two to four portions of tissue into sterile, leakproof, freezable container. For scabs, aseptically place scrapings/material into sterile, leakproof freezable container. For vesicular fluid, collect fluid from separate lesions onto separate sterile swabs. Always include material from base of each vesicle. These specimens are transported at 4 C within 6 hours, or stored at -20 to -70 C.
Which is estimated to have killed more people: plague or smallpox?
Plague is estimated to have killed >25 million. Smallpox is estimated to have killed ~500 million.
What are the 2 variants of smallpox, and what are their mortality rates?
Two variants of smallpox are known: variola major, which is associated with a higher mortality rate of 15%–40%, and variola minor, which causes a milder disease and is associated with a mortality rate of only 1%.
Is the aerosol infective dose for smallpox low or high?
It is currently assumed that an aerosol infective dose is low and presumably ranges from 10–100 organisms.
Postexposure immunization with smallpox vaccine (vaccinia virus) is effective and is recommended if given within ___ days of exposure.
Postexposure immunization with smallpox vaccine (vaccinia virus) is effective and is recommended if given within 3 days of exposure. However, even if more than 3 days elapse, vaccination and vaccinia immune globulin may provide protection.
Clinical presentation of smallpox.
Smallpox is transmitted by large or small respiratory droplets, and by contact with skin lesions or secretions. Patients are considered more infectious if they are actively coughing. The incubation period is typically 12 days, with a range of 10–12 days. Clinical illness begins with a 2 to 3 day period of vague symptoms such as malaise, fever, headache, chills, and backache. The fever can last as long as 5 days or may be as short as 1 day. After the fever, an exanthem (eruption of skin or rash) appears that undergoes papular, pustular, and crustular stages. The latter falls off 2–4 weeks after the initial lesion and leaves a pink scar. An important characteristic of smallpox is that lesions in affected areas appear in the same state.
How can chickenpox and smallpox be distinguished based on the skin lesions?
An important characteristic of smallpox is that lesions in affected areas appear in the same state. This differs from chickenpox, where lesions are not synchronous and occur in crops. Smallpox lesions are distributed centrifugally (more numerous on the face and extremities than on the trunk), unlike chickenpox. Hence, the smallpox exanthem is very characteristic and is a useful diagnostic tool.
What is the fatality rate for smallpox in unvaccinated patients and vaccinated patients?
The fatality rate is 15%–40% in unvaccinated patients and <1% in those vaccinated.
During what time period are patients with smallpox infectious?
Patients with smallpox are infectious as soon as a rash occurs and remain infectious until scabs fall off, approximately 3 weeks later. Generally, respiratory droplets become infectious earlier than skin lesions. In hospitals, both airborne and contact precautions are required to prevent contagion.
What is the role of the Level A laboratory in identification of Venezuelan equine encephalitis or other encephalitides?
Submit samples immediately to public health laboratory for evaluation and referral. Level A laboratory responsibility is limited to advising medical staff on specimen selection, packing and shipping sample, and communicating with reference laboratory. Serum and CSF are taken for or culture, PCR, or serologies (ELISA, FA, etc.). Nasal, respiratory samples (including induced samples) are taken for culture and PCR. Other specimens such as biopsy, autopsy, stool, etc., are sent for pathology, culture, hematology/chemistry analysis, etc. All samples are transported at 4 C within 6 hours or stored at -20 to -70 C.
Venezuelan equine encephalitis is clinically indistinguishable from other encephalitis viruses such as St Louis encephalitis, Eastern and Western equine encephalitis, Japanese B-type encephalitis, Russian Far East encephalitis, and even West Nile encephalitis virus. Why are these other agents not as high on the list of potential bioterror weapons as VEE?
Many can be, but the attack rate, that is, the number of people who would probably get the disease after being exposed to the agent, is much lower than for VEE, which has an attack rate of about 100%.
How many serologically distinct Venezuelan equine encephalitis viruses are there? Which are important pathogens for humans?
Eight serologically distinct viruses exist, but only two are important pathogens for humans: variants A/B and C.
What is the role of the Level A laboratory in identification of the viral hemorrhagic fevers, such as Crimean Congo, Ebola, and yellow fever?
Submit samples immediately to public health laboratory for evaluation and referral. Some viruses are highly infectious; avoid manipulation; if necessary, use Biological Safety Level-3 practices. Level A laboratory responsibility is limited to advising medical staff on specimen selection, packing and shipping sample, and communicating with reference laboratory. Serum is taken for culture, PCR, or serologies (ELISA, HI, FA, etc.). Other specimens such as biopsy, autopsy, etc., are taken for for pathology, culture, hematology/chemistry analysis, etc. Specimens are transported at 4 C within 6 hours, or stored at -20 to -70 C.
Any one of the following hemorrhagic viruses can be weaponized via aerosol delivery except for which one? Ebola, Marburg, Lassa fever, Argentine (Junin), Bolivian (Machupo), Crimean Congo, Hantavirus, Rift Valley fever, Dengue, Yellow fever.
Dengue, which is transmissible only via mosquito. In general, VHFs are very difficult to weaponize because there is no real carrier state.
What are the natural means of transmission for the following viral hemorrhagic fevers? Ebola, Marburg, Lassa fever, Argentine (Junin), Bolivian (Machupo), Crimean Congo, Hantavirus, Rift Valley fever, Dengue, Yellow fever.
Ebola: contact. Marburg: contact. Lassa fever: contact. Argentine (Junin): contact and aerosol. Bolivian (Machupo): contact and aerosol. Crimean Congo: ticks and contact. Hantavirus: contact and aerosol. Rift Valley fever: mosquito and aerosol. Dengue: mosquito. Yellow fever: mosquito.
Which viral hemorrhagic fever is transmitted by ticks (and contact)?
Crimean Congo.
True or false. Ricin can be delivered effectively by injection, ingestion, and inhalation.
True.
What infectious disease risks are an indefinite deferral from allogeneic blood donation?
Viral hepatitis after 11th birthday. Positive test for hepatitis B surface antigen. Repeat reactive test for anti-HBc on more than one occasion. Clinical or laboratory evidence of HCV, HTLV, or HIV infection by current FDA regulations. Previous donation associated with hepatitis, HIV, or HTLV transmission. Behavioral risk factors for HIV infection according to current FDA guidance. History of babesiosis or Chagas’ disease. Stigma of parenteral drug use. Injection of nonprescription drugs. Risk of vCJD according to current FDA guidelines.
What infectious disease risks are a 12-month deferral from allogeneic blood donation?
Mucous membrane exposure to blood. Nonsterile skin or needle penetration. Sexual contact with an individual with a confirmed positive test for hepatitis B surface antigen. Sexual contact with an individual with viral hepatitis. Sexual contact with an individual with HIV infection or at higher risk for HIV infection. Incarceration in a correctional institution for longer than 72 consecutive hours. History of syphilis or gonorrhea.
2010 blood donor infectious disease testing required entities.
Hep B surface antigen (EIA). Hep B core antibody (EIA). Hep C virus antibody (EIA). HIV-1 and HIV-2 antibodies (EIA) (combined HIV p24 antigen, HIV-1 antibodies, and HIV-2 antibodies acceptable). HTLV-I and HTLV-II antibodies (EIA). Trypanosoma cruzi antibodies (EIA). Serologic test for syphilis. Hep C RNA (NAT). HIV RNA (NAT). West Nile virus DNA (NAT).
Anaplasma phagocytophilum. What is the old name? What disease does it cause?
Anaplasma phagocytophilum (formerly Ehrlichia phagocytophilum) is a gram-negative rickettsial bacterium that is unusual in its tropism to neutrophils. It causes anaplasmosis in sheep and cattle, also known as tick-borne fever and pasture fever, and also causes the zoonotic disease human granulocytic anaplasmosis.
True or false. HIV infection is a risk factor for TA-GVHD.
False. HIV infection, although it may cause marked T cell dysfunction, does not increase the risk of TA-GVHD.
What are the 2010 risk estimates for per-unit risk of transfusion-associated infectious disease transmission for: HIV, HBV, HCV, HTLV-I/II, and West Nile virus?
HIV - 1:1,467,000. HBV - 1:280,000-1:357,000. HCV - 1:1,149,000. HTLV-I/II - 1:641,000-1:1,900,000. West Nile virus - ~1:7,000,000.
Approximately __% of blood donors are CMV seropositive, although the estimated risk of transmission by a seropositive transfusion is about __%.
Approximately 50% of blood donors are CMV seropositive, although the estimated risk of transmission by a seropositive transfusion is about 1%.
Most acute West Nile virus infections are asymptomatic, with a febrile illness occurring in about 1 in __ infections and neuroinvasive disease in about 1 in __ infections.
Most acute West Nile virus infections are asymptomatic, with a febrile illness occurring in about 1 in 5 infections and neuroinvasive disease in about 1 in 150 infections.
For West Nile virus, what is the natural reservoir and what is the vector?
Birds are the natural reservoir, with mosquitoes serving as the vector of transmission. Humans are an accidental host, with infection occurring during times of mosquito activity.
Babesia species are endemic in North American mammals and are transmitted by ticks of the genus ___.
Babesia species are endemic in North American mammals and are transmitted by ticks of the genus Ixodes.
If a swab must be used to collect a microbiologic specimen, what type is the best?
A polyester-tipped swab on a plastic shaft is acceptable for most organisms. Calcium alginate should be avoided for collection of samples for viral culture, because it could inactivate herpes simplex virus (HSV); cotton may be toxic to Neisseria gonorrhoeae; and wooden shafts should be avoided, because the wood may be toxic to Chlamydia trachomatis. Swabs are not optimal for detection of anaerobes, mycobacteria, or fungi, and they should not be used when these organisms are suspected. An actual tissue sample or fluid aspirate is always superior to a swab specimen for the recovery of pathogenic organisms.
What types of microbiologic specimens should be refrigerated if not transported immediately to the lab, and what specimens should be held at room temp and not refrigerated?
After collection, specimens should be placed in a biohazard bag and transported to the laboratory as soon as possible. If a delay is unavoidable, urine, sputum and other respiratory specimens, stool, and specimens for detection of C. trachomatis or viruses should be refrigerated to prevent overgrowth of normal flora. CSF and other body fluids, blood, and specimens collected for recovery of N. gonorrhoeae should be held at room temperature, because refrigeration adversely affects recovery of potential pathogens from these sources.
At a minimum, what microbiologic specimens should be handled in a biological safety cabinet?
Optimally, all specimen containers but, at a minimum, those containing respiratory secretions and those submitted specifically for detection of mycobacteria or fungi should be opened in a biological safety cabinet. Specimens collected for virus isolation should be handled in a biological safety cabinet to prevent contamination of the cell cultures.
When is the optimal time to draw blood for cultures when bacteremia or fungemia is suspected?
The optimal time to draw blood for cultures when bacteremia or fungemia is suspected is just before a chill but, because this is not predictable, most blood cultures are collected after the onset of fever and chills.
What is the volume of blood that should be drawn for blood cultures for adults and children?
In adults with bacteremia, the number of colony-forming units (CFU) per milliliter of blood is frequently low. Therefore, for adults, collecting 20–30 mL of blood per culture set is strongly recommended. In infants and children, the concentration of microorganisms in blood is higher, and collection of 1–5 mL of blood per culture is adequate.
What are frequent blood culture contaminant organisms?
Organisms such as the coagulase-negative staphylococci, viridans streptococci, corynebacteria, Bacillus species, and Propionibacterium species are frequent blood culture contaminants but may also be true pathogens.
What are some approaches that have been used to counteract factors that impede recovery of microorganisms from blood for cultures?
Diluting the blood specimen in broth medium in a 1:10 ratio provides optimal neutralization of the serum bactericidal activity. Incorporating 0.02–0.05% sodium polyanethol sulfonate in the blood culture medium inhibits coagulation, phagocytosis, and complement activation, and inactivates aminoglycosides. Methods that counteract the presence of antimicrobial agents are available as well.
What are the 2 commercial manual blood culture systems that are available, and what are some automated blood culture systems that are commercially available?
Two commercial manual blood culture systems are available: the biphasic system and the lysis-centrifugation system. Examples of automated systems include one based on colorimetric detection of CO2 produced during microbial growth, one based on fluorescent technology and pH, and one that is based on measuring gas consumption and/or gas production.
How is Borrelia diagnosed in the microbiology laboratory?
Infections with species of Borrelia, except Borrelia burgdorferi (the etiologic agent of Lyme disease, most commonly diagnosed serologically), are diagnosed by detecting spirochetes in the peripheral blood during febrile periods. Organisms are visualized in wet preparations made by mixing a drop of blood with a drop of sodium citrate, and examining it with light- or dark-field microscopy, and in thin and thick blood films stained with Wright’s or Giemsa stains, examined by light microscopy.
What are the two methods that may be used to recover mycobacteria from blood specimens?
With the lysis–centrifugation technique, (1) a concentrate is prepared, (2) the sediment is inoculated to solid and/or liquid media, and (3) the cultures are incubated for up to 8 weeks. An alternative and perhaps more rapid approach is direct inoculation of the liquid medium developed by the manufacturer of automated and semiautomated broth culture systems specifically for recovery of mycobacteria.
How soon are positive blood cultures usually detected for aerobic and anaerobic organisms, and how soon is identification usually available?
With the lysis–centrifugation technique, (1) a concentrate is prepared, (2) the sediment is inoculated to solid and/or liquid media, and (3) the cultures are incubated for up to 8 weeks. An alternative and perhaps more rapid approach is direct inoculation of the liquid medium developed by the manufacturer of automated and semiautomated broth culture systems specifically for recovery of mycobacteria.
How soon are positive blood cultures usually detected for aerobic and anaerobic organisms, and how soon is identification usually available?
Positive blood cultures containing commonly isolated aerobic organisms are usually detected within 12–36 hours of incubation. The initial report is a Gram stain report only. Identification and susceptibility results can be expected within 24–48 hours after the Gram stain report. Cultures containing anaerobes are usually not detected for 48–72 hours, and identification is not available for 3–4 days after that. Fastidious organisms, such as those found in the HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) may not be detected until 3–5 days.
What is BCG? What is it used for and what is the mechanism of action?
Bacille Calmette–Guerin is a live-attenuated strain of Mycobacterium bovis developed in 1921 as a vaccine for tuberculosis. The first published reports of its use in the bladder were in 1976. Intravesical BCG therapy has been demonstrated to reduce the recurrence rate and the risk of progression to muscle-invasive disease in patients with CIS (BCG is the gold standard for treatment of urothelial CIS), as well as superficial bladder tumors. High-risk patients treated with BCG following TURBT have lower cystectomy rates. The mechanism of action is induction of a massive influx of inflammatory cells and production of cytokines in the bladder mucosa and lumen that leads to an immune response against tumor cells. An intact immune system is a necessary prerequisite to successful BCG therapy.
Epidemiology of primary effusion lymphoma.
The majority of cases occur in young to middle-aged males, either homosexual or bisexual, with HIV infection and severely immunocompromised. However, it can also occur in HIV-negative individuals who are immunocompromised as a result of solid-organ transplantation or cirrhosis. In rare instances, PEL can affect elderly individuals who are otherwise immunocompetent but live in geographic areas with high HHV8 prevalence, such as the Mediterranean region; these cases may be EBV negative.
P blood group system. Null phenotypes p and P^k (P1^k and P2^k), because they lack P antigen, they are resistant to what microorganism?
Parvovirus B19.
An autoantibody with anti-___ specificity is seen in patients with paroxysmal cold hemoglobinuria, a clinical syndrome that may occur in children following viral infection.
An autoantibody with anti-P specificity is seen in patients with paroxysmal cold hemoglobinuria, a clinical syndrome that may occur in children following viral infection.
In the P blood group system, what is auto-anti-P?
An autoantibody with anti-P specificity is seen in patients with paroxysmal cold hemoglobinuria, a clinical syndrome that may occur in children following viral infection. In PCH, autoanti-P is an IgG, biphasic hemolysin capable of binding RBCs at colder temperatures, followed by intravascular hemolysis at body temperature. This characteristic can be demonstrated in vitro in the Donath-Landsteiner test.
Several P blood group antigens are receptors for microbial pathogens. Give examples.
The P blood group antigen is the receptor for parvovirus B19. Pk can bind HIV and may confer resistance to HIV infection. The P1 and Pk antigens are receptors for shiga toxins, produced by Shigella dysenteriae and enterohemorrhagic Escherichia coli (EHEC) strains. In addition to gastroenteritis, EHEC infection is the most common cause of community-acquired hemolytic-uremic syndrome, probably reflecting toxin binding to Pk antigen on glomerular vascular endothelium and platelets. P, Pk, and LKE blood group antigens on uroepithelium are cell receptors for P-fimbriae, a bacterial adhesin and colonization factor expressed on uropathogenic E. coli strains. The Pk antigen also serves as a receptor for Streptococcus suis and Pseudomonas aeruginosa.
What is the relationship between the Lewis blood group antigens and susceptibility to/resistance against particular infectious organisms?
H. pylori binds H, Leb, and Ley antigens via BabA recognition of a terminal Fucα1–2Gal epitope and appears to explain the increased incidence of ulcers and stomach cancer among blood group O secretors. A Lewis null and/or nonsecretor phenotype has also been linked with a higher incidence of recurrent Candida vaginitis and urinary tract infection. A Le (a−b−) phenotype is associated with an increased incidence of heart disease. Conversely, a nonsecretor phenotype protects against Norovirus infection.
Why is there increased incidence of ulcers and stomach cancer among blood group O secretors?
H. pylori binds H, Leb, and Ley antigens via BabA recognition of a terminal Fucα1–2Gal epitope.
What blood group system antigen has a relationship to Plasmodium vivax?
P. vivax binds to the amino-terminal domain of DARC (Duffy Antigen Receptor for Chemokines)/the Duffy glycoprotein. Hence, Fy null individuals are resistant to most P. vivax strains.
Mycoplasma pneumoniae infection is associated with cold agglutinin disease secondary to anti-__, and infectious mononucleosis is associated with cold agglutinin disease secondary to anti-__.
Mycoplasma pneumoniae infection is associated with cold agglutinin disease secondary to anti-I, and infectious mononucleosis is associated with cold agglutinin disease secondary to anti-i.
Infectious meningitis is divided into acute, subacute, and chronic clinical syndromes, based on duration of symptoms. What are probable pathogens based on these categories?
Acute (onset/duration of <24 hours): Pyogenic bacteria. Subacute (onset/duration of 1-7 days): Enteroviruses, pyogenic bacteria. Chronic (persisting at least 4 weeks): M. tuberculosis, T. pallidum, Brucella sp., L. interrogans, B. burgdorferi, C. neoformans, C. immitis, H. capsulatum.
What are common bacterial causes of acute meningitis by age, for neonates-3 months, 4 months-6 years, 6-45 years, and >45 years?
Neonates-3 months: Group B streptococcus, E. coli, L. monocytogenes (Listeria can cause meningitis in immunocompromised individuals in all age groups). 4 months-6 years (Incidence of meningitis due to HIB in the US has declined dramatically due to vaccination): S. pneumoniae. 6-45 years: N. meningitidis. >45 years: S. pneumoniae, L. monocytogenes, Group B streptococcus.
For CSF, in addition to smears stained with the Gram stain and bacterial culture, the supernatant of a centrifuged specimen or the original fluid may be used to perform latex agglutination tests for detection of antigens of ___.
For CSF, in addition to smears stained with the Gram stain and bacterial culture, the supernatant of a centrifuged specimen or the original fluid may be used to perform latex agglutination tests for detection of antigens of Streptococcus agalactiae, S. pneumoniae, some serotypes of Neisseria meningitidis, Escherichia coli (the K1 capsular antigen cross-reacts with that of N. meningitidis type B), and H. influenzae type b.
Two types of rapid tests are available for diagnosis of meningitis caused by C. neoformans: ___.
Two types of rapid tests are available for diagnosis of meningitis caused by C. neoformans: those specific for the capsular antigen (latex agglutination and ELISA) and the nonspecific India ink preparation, which allow visualization of encapsulated yeast cells.
Currently, nucleic acid amplification tests are used most often for diagnosis of viral infections of the central nervous system. Other diagnostic methods are ___ (primarily for detection of enteroviruses, although PCR is preferred) and ___ for viruses that cause encephalitis (western equine, eastern equine, Venezuelan equine, St Louis, Japanese, and La Crosse and West Nile).
Currently, nucleic acid amplification tests are used most often for diagnosis of viral infections of the central nervous system. Other diagnostic methods are conventional cell culture (primarily for detection of enteroviruses, although PCR is preferred) and serologic tests for viruses that cause encephalitis (western equine, eastern equine, Venezuelan equine, St Louis, Japanese, and La Crosse and West Nile).
The HIV-(1 or 2?) family is divided into main (M), outlier (O), and non-M non-O (N) groups.
The HIV-1 family is divided into main (M), outlier (O), and non-M non-O (N) groups.
The HIV-1 family is divided into main (M), outlier (O), and non-M non-O (N) groups. Group M has 11 distinct subtypes or clades (A-K). Which clade is most common in the US?
In the US, clade B is almost exclusively prevalent.
HIV testing is accomplished by ELISA, and repeat-reactive tests are confirmed by western blot testing for the presence of antibodies directed against the HIV proteins of the ___, ___, and ___ genes.
HIV testing is accomplished by ELISA, and repeat-reactive tests are confirmed by western blot testing for the presence of antibodies directed against the HIV proteins of the gag, pol, and env genes.
After initial infection and propagation of HIV in lymph nodes, a blood donor becomes infectious (defined as day 0), with HIV RNA being detectable in plasma and platelets on days __ - __. HIV DNA is detectable in leukocytes at days __ - __, and HIV antibodies are detectable between days __ and __.
After initial infection and propagation of HIV in lymph nodes, a blood donor becomes infectious (defined as day 0), with HIV RNA being detectable in plasma and platelets on days 14-15. HIV DNA is detectable in leukocytes at days 17-20, and HIV antibodies are detectable between days 20 and 25.
Why is the HIV p24 antigen testing no longer required on donated blood?
After the introduction of testing for HIV RNA by NAT, p24 antigen testing no longer provided added benefit in reducing the risk of transfusion-transmitted HIV, and the FDA allowed discontinuation of antigen testing in the US as long as HIV NAT was being used. And also, HIV-1/HIV-2 antibody tests are performed as well.
AABB Standards requires the use of what 2 tests to test donors for HBV infection?
AABB Standards requires the use of HBsAg and anti-HBc to test donors for HBV infection.
What are the two available test methods for anti-HBc?
A solid-phase inhibition immunoassay, and a direct antiglobulin assay.
In the US, HBsAg and anti-HBc testing is required to screen blood donors for HBV. How does Japan modify this screening?
Japan, a country with moderate prevalence of HBV infection, modifies anti-HBc screening to accept donor with high amounts of anti-HBs, if also HBV NAT negative, because presence of anti-HBs in the absence of detectable HBV usually signifies a resolved infection and absence of circulating virus.
AABB Standards requires the use of what 2 tests to test donors for HCV infection?
AABB Standards requires the use of anti-HCV and HCV RNA NAT to test donors for HCV infection.
What is the primary screening test for anti-HCV when testing blood donors? What is done when this is positive?
A third-generation antiglobulin EIA is the primary screening test for antibodies to HCV. If the initial EIA is positive, the test is repeated. If the second EIA is “repeat reactive,” a confirmatory/supplemental test is performed, which is currently a recombinant immunoblot assay (RIBA) against HCV antigens, which is FDA-approved for supplemental testing.
In screening blood donors for anti-HCV, EIAs are performed. For donors that have “repeat reactive” EIA, a confirmatory/supplemental test is performed, which is currently a recombinant immunoblot assay (RIBA) against HCV antigens, which is FDA-approved for supplemental testing. What is done when the RIBA is positive and what is done when it is negative?
A donor with a reactive RIBA is permanently deferred from donating and is considered to be infected with HCV. Of EIA repeatedly reactive donors, 37% have a non-reactive or indeterminate RIBA test result and are rarely infectious for HCV. Whether or not the RIBA is reactive, if a blood donor is repeatedly reactive for anti-HCV by EIA, the donation cannot be used for transfusion. However, a donor who has a non-reactive RIBA and reactive EIA (without HCV NAT positivity) can be considered for re-entry by application to the FDA.
What are the 2 commercially available, FDA-approved HCV NAT procedures used for screening blood donors?
A PCR test performed on RNA tested by chemical methods on mini-pools of 16-24 donor blood samples; and a transcription-mediated amplification (TMA) test on nucleic acid preparations in a solid phase (probe-capture) method, also performed on mini-pools of donor samples. Both test methods are sensitive and specific and perform equally well in identifying HCV RNA.
What testing type, timing and algorithm is used for screening blood donors for West Nile virus?
A minipool NAT is done, with a recommended trigger for implementing individual NAT when two presumed viremic donors (PVD; defined as an initial reactive donor that repeats on the original sample) occur within a 7-day period; MP-NAT is resumed after 7 days without PVD donations or ongoing regional activity, or at the medical director’s direction.
Screening blood donors for West Nile virus is done by NAT. What is the confirmatory test?
WNV infectivity of the donor is confirmed by either repeat NAT reactivity on a follow-up sample, or IgM and IgG antibody reactivity with neutralization testing on either the original (index) sample or a follow-up sample.
What cell type(s) do HTLV-1 and HTLV-2 infect?
HTLV-1 predominantly infects CD4+ lymphocytes while HTLV-2 preferentially infects CD8+ lymphocytes (and, to a lesser extent, infects CD4+ lymphocytes, B lymphocytes and macrophages).
How is HTLV screened for in blood donors?
The FDA has approved the use of EIAs which detect both HTLV-1 and -2 antibodies. These tests typically use viral lysates as the capture reagent, and adherent donor antibodies are identified with an antiglobulin conjugate. There are no licensed confirmatory or supplemental tests for the HTLV-1/2 EIAs. One approach to supplemental testing to confirm a reactive anti-HTLV test is to repeat the test using an alternate manufacturer’s EIA. Western blot and radioimmunoprecipitation (RIPA) tests are available.
Blood donors are screened for HTLV-1 and -2 antibodies by EIA. What is the confirmatory test for a positive screening EIA?
There are no licensed confirmatory or supplemental tests for the HTLV-1/2 EIAs. One approach to supplemental testing to confirm a reactive anti-HTLV test is to repeat the test using an alternate manufacturer’s EIA. Western blot and radioimmunoprecipitation (RIPA) tests are available.
What are the 3 indications for leukoreduction of blood products, 2 potential indications, and 1 controversial indication?
Indications: Decreasing incidence of febrile non-hemolytic transfusion reactions. Decreasing incidence of HLA alloimmunization. Decreasing CMV transmission. Potential indications: Decreasing other HHV (i.e. EBV, HHV-6, HHV-7, HHV-8) transfusion transmitted infections. Possible decrease in transmission of prion disease. Controversial indication: Decreasing TRIM (Transfusion-Related ImmunoModulation).
The Cromer blood group system antigens are present on DAF (CD55), which is widely expressed on tissues and in secretions. For what microorganisms is CD55 a receptor for?
Echovirus, coxsackie B virus, and uropathogenic and intestinal E. coli strains bearing Afa/Dr and X adhesins.
Antibodies to the I blood group system. What Ig isotype? Auto and alloantibodies?
Anti-I and anti-i are antibodies of IgM isotype, reactive at room temperature. Autoantibodies to I are relatively common and are usually low-titered cold agglutinins. Some anti-I can have IH specificity, reacting stronger with group O and A2 RBC. Although generally benign, hemolysis secondary to high-titered anti-I is observed in cold autoimmune hemolytic anemia (CAIHA). CAIHA can occur in the setting of malignancy and occasionally infection (e.g., Mycoplasma pneumoniae). These antibodies display high thermal amplitude, often agglutinating RBCs at temperatures of 30°–34° C. In contrast, alloanti-I is relatively rare and is found as a naturally occurring antibody in iadult individuals.
In what conditions can secondary WAIHA be seen?
Secondary WAIHA is often observed in autoimmune diseases (frequently systemic lupus erythematosus), in lymphoproliferative disorders, and following viral infections.
What are the clinical significances of the following cold red cell autoagglutinins: I, i, Pr, P, H, IH?
I: Acute CAD associated with Mycoplasma pneumoniae with antibody titers >1000 at 4° C. i: Acute CAD associated with mononucleosis. Pr: Rare cause of CAD. P: PCH associated with certain viral infections in children. H: Benign except as alloantibody in Bombay phenotype. IH: Benign.
Cold agglutinin disease (CAD) accounts for about __% of total cases of AIHA.
Cold agglutinin disease (CAD) accounts for about 20% of total cases of AIHA. As with WAIHA, CAD may be idiopathic or secondary following infection or malignancy.
Which infectious processes can result in a leukemoid reaction, and which can result in leukopenia?
Some patients with Clostridium difficile infection or tuberculosis may manifest a leukemoid reaction with a WBC count greater than 50,000/mL. Conversely, typhoid fever, brucellosis, tularemia, rickettsial diseases, ehrlichiosis, leishmaniasis, and some cases of Staphylococcus aureus infection may be associated with leukopenia.
Infectious lymphocytosis (generally 20,000–50,000/mL small, mature-appearing lymphocytes) is mainly a disease of children. What infectious entities can cause it?
It may be related to coxsackievirus A or B6, echovirus, and adenovirus 12, and is rarely associated with splenomegaly or lymphadenopathy. Infection with EBV can cause atypical lymphocytosis (large and reactive lymphocytes with abundant basophilic cytoplasm) and lymphadenopathy. HTLV-1 may produce a transient lymphocytosis (usually <20,000/mL) with fever, rash, and lymphadenopathy. In contrast to most other bacterial infections, pertussis (whooping cough) is frequently accompanied by lymphocytosis.
What is the purpose of adding 0.025%-0.050% sodium polyanethol sulfonate to nutrient broth media for the collection of blood cultures?
SPS is used in most commercial blood culture products because it functions as an anticoagulant and prevents phagocytosis and complement activation. In addition, SPS neutralizes aminoglycoside antibiotics.
Semisolid transport media such as Amies, Stuart, or Cary-Blair are suitable for the transport of swabs for culture of most pathogens except for Neisseria gonorrhoeae. Why?
Specimens for culture of N. gonorrhoeae are best if plated immediately or transported in a medium containing activated charcoal to absorb inhibitory substances that hinder their recovery.
What is the media of choice for recovery of Vibrio cholerae from a stool specimen?
Thiosulfate-citrate-bile-sucrose (TCBS) agar is used to grow V. cholerae, which appear as yellow colonies as a result of the use of both citrate and sucrose. Alkaline peptone water (APW) broth is used as an enrichment broth and should be subcultured to TCBS agar for further evaluation of Vibrio colonies.
Colistin-nalidixic acid agar is used primarily for the recovery of what type of organisms?
CNA agar inhibits the growth of gram-negative bacteria and is used to isolate gram-positive cocci from specimens. This medium is especially useful for stool and wound cultures because these may contain large numbers of gram-negative rods.
Under what conditions should N. gonorrhoeae be cultured in?
N. gonorrhoeae cultures must be incubated in 3-7% CO2 at 35 C. Cultures should be held a minimum of 48 hours before being considered negative.
What is modified Thayer-Martin agar contain, and what is it used for?
MTM is a chocolate agar containing vancomycin, colistin, nystatin, and trimethoprim. These permit isolation of N. gonorrhoeae in specimens containing large numbers of gram-negative bacteria, including commensal Neisseria species.
What organism is cycloserine-cefoxitin-fructose agar used for the recovery of?
CCFA is used for recovery of C. difficile from stool cultures. Cycloserine and cefoxitin inhibit growth of gram-negative coliforms in the stool specimen. C. difficile ferments fructose, forming acid that, in the presence of neutral red, causes the colonies to become yellow.
What organism is deoxycholate agar useful for the isolation of?
Enterobacteriaceae. DCA inhibits gram-positive organisms. N. gonorrhoeae and N. meningitidis are too fastidious to grow on DCA. Citrate and deoxycholate salts inhibit growth of gram-positive bacteria.
What organism is xylose lysine deoxycholate agar used for the recovery of?
XLD agar is a highly selective medium used for recovery of Enterobacteriaceae from gastrointestinal specimens. XLD agar is selective for gram-negative coliforms because of a high concentration (0.25%) of deoxycholate, which inhibits gram-positive bacteria. In addition, XLD is differential for Shigella and Salmonella spp.
True or false. Haemophilus influenzae requires V factor, and Haemophilus parainfluenzae requires V and X factors.
False. Haemophilus influenzae requires V and X factors, and Haemophilus parainfluenzae requires V factor.
What are the 8 tubercle bacilli that make up the M. tuberculosis complex?
The tubercle bacilli that make up the M. tuberculosis complex (MTBC; Mycobacterium tuberculosis, Mycobacterium bovis, M. bovis Bacille Calmette-Guérin strain [BCG], Mycobacterium caprae, Mycobacterium pinnipedii, Mycobacterium africanum, Mycobacterium microtii, and Mycobacterium canettii) are the etiologic agents of human tuberculosis (TB).
How are multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis defined?
Among new cases of TB, approximately 5% (or 500,000) worldwide are due to MDR-TB, defined as tubercle bacilli that are resistant to rifampin and isoniazid. MDR-TB does not respond to the standard 6-month treatment regimen and may require up to 2 years of treatment with drugs that are more toxic than first-line agents and about 100 times more costly. Mismanagement of drugs used to treat MDR-TB can result in XDR-TB, defined as MDR-TB plus resistance to any fluoroquinolone and any second-line injectable antituberculosis agent (e.g., amikacin, kanamycin, capreomycin).
What are the pathophysiologic processes that occur with M. tuberculosis complex infection?
The usual host response to infection with MTBC is activation of the cell-mediated immune system. During primary (initial) infection, inhaled bacilli travel to the alveolar spaces, where they are ingested by resident macrophages. These macrophages are unable to kill the bacilli, which multiply intracellularly during the first several days after infection. Macrophages infected with mycobacteria migrate to regional tracheobronchial lymph nodes and present sensitizing antigen(s) to immunocompetent T cells, or they enter the lymphatics and blood and travel back to the lungs (primarily the apices) and to distant organs such as lymph nodes, kidneys, epiphyseal areas of the long bones, vertebral bodies, and meninges, where bacilli continue to multiply until the cellular immune response is activated. Immunocompetent T cells migrate from regional lymph nodes to the site of infection in the lung, releasing chemotactic, migration-inhibitory, and mitogenic cytokines. Cytokines and lytic enzymes released by activated macrophages also contribute to concomitant local tissue destruction. Over time, the activated T cell population declines and is replaced by long-lived memory immune T cells, which protect against reinfection with MTBC and provide some cross-protection against infection with other mycobacteria.
Candida ___ consists of small, uniform, round budding yeast forms surrounded by clear halos on Pap stain. Unlike other Candida species, it does not form pseudohyphae in vivo or in culture.
Candida (previously Torulopsis) glabrata consists of small, uniform, round budding yeast forms surrounded by clear halos on Pap stain. Unlike other Candida species, it does not form pseudohyphae in vivo or in culture.
What component of the virus is in the HPV vaccines?
The major HPV capsid protein L1.
HPV-related head and neck squamous cell carcinomas are restricted in distribution to which of the following sites: tonsils, nose, hard palate, buccal mucosa, oral tongue, base of tongue, lip, oropharynx?
Oropharynx, tonsils, and base of tongue.
What is the most common cause of renal failure in cirrhotic patients?
Spontaneous bacterial peritonitis.
What are 6 general causes of conjugated neonatal hyperbilirubinemia?
Biliary obstruction (extrahepatic biliary atresia). Sepsis or TORCH infection. Neonatal hepatitis (idiopathic, Wilson disease, alpha-1 antitrypsin deficiency). Metabolic disorders (galactosemia, hereditary fructose intolerance, glycogen storage disease). Inherited disorders of bilirubin transport (Dubin-Johnson syndrome, Rotor syndrome). Parenteral alimentation.
Out of viral, toxic, ischemic, and alcoholic hepatitis, which tend to have AST:ALT over 1?
The AST:ALT is over 2 in 80% of patients with toxic, ischemic, and alcoholic hepatitis. It is usually <1 in viral hepatitis.
Out of alcoholic hepatitis, acute hepatitis A, acute hepatitis B, and acute hepatitis C, in which conditions does jaundice occur most frequently?
Jaundice occurs in 70% of patients with alcoholic hepatitis and acute hepatitis A, and occurs in 20-30% of patients with acute hepatitis B and acute hepatitis C.
What is macroamylasemia?
A benign acquired condition (associated with celiac disease, lymphoma, HIV infection, monoclonal gammopathy, rheumatoid arthritis, and ulcerative colitis) with an incidence of ~1%, in which apparently healthy individuals have markedly elevated serum amylase levels (with low urine amylase levels), due to Ig-amylase complexes.
What are uncomplicated and complicated UTIs?
Uncomplicated UTI often refers to cases of cystitis in healthy young adult nonpregnant females without anatomic genitourinary anomalies. Some authors also include pyelonephritis in healthy young adult females, cystitis in young adult males, and cystitis in healthy postmenopausal women, Complicated UTI often refers to one arising in association with pregnancy, diabetes, stone, structural genitourinary anomalies, spinal injury, children, and males.
What is eosinophiluria suggestive of?
Acute interstitial nephritis, not UTI.
What organisms cause the most community-acquired UTIs?
E. coli causes ~80%. S. saprophyticus is a very common cause in young sexually active women, and causes ~15% of community-acquired UTIs. Other enterobacteriaceae, especially Klebsiella spp and Enterobacter spp, cause a significant number of the remaining cases.
Culture-negative UTIs are mostly due to what 3 organisms?
Ureaplasma urealyticum, Chlamydia spp, or Mycoplasma hominis.
Corynebacterium group __ appears to be a significant cause of hospital-acquired UTI.
Corynebacterium group D2 appears to be a significant cause of hospital-acquired UTI.
Bacteria can cause inflammatory (colitic) or noninflammatory infectious diarrhea. List some causes of each.
Noninflammatory bacterial diarrhea: Vibrio spp, E. coli (especially ETEC and EPEC), C. perfringens, S. aureus, and B. cereus. Inflammatory bacterial diarrhea: C. difficile, Salmonella, Shigella, Campylobacter.
What clinical features suggest a bacterial (as opposed to viral) cause of infectious diarrhea?
Prolonged (>5 days) illness and fever.
Diarrhea with blood, especially without fecal neutrophils, suggests what 2 causes?
Enterohemorrhagic E. coli (O157:H7). This may also be seen with amebiasis (capable of destroying leukocytes).
What are the most common bacterial causes of infectious diarrhea in travelers to South and Central America, and in travelers to the far East?
South and Central America: Varieties of E. coli (ETEC, EIEC). The far East: Campylobacter, Salmonella, Shigella.
What is the most common cause of death from food-borne illness in the US?
Salmonella.
What is the most common cause of viral gastroenteritis in children and adults?
Pediatric: Rotavirus. Adult: Norwalk virus.
HPV-related head and neck squamous cell carcinomas are restricted in distribution to which of the following sites: tonsils, nose, hard palate, buccal mucosa, oral tongue, base of tongue, lip, oropharynx?
Oropharynx, tonsils, and base of tongue.
For the following risk/host factors, what are likely agents for pneumonia? COPD, alcoholic, neutropenia, animal exposure, sandstorm exposure, bronchiectasis/CF, community-acquired PNA in immunocompetent healthy adults, elderly nursing home tenants, hospitalized ventilated patients.
COPD: H. influenzae, M. catarrhalis, L. pneumophila. Alcoholic: S. pneumoniae, anaerobes, GN aerobic bacilli. Neutropenia: Aerobic GN bacilli, Animal exposure: C. burnetii, C. psittaci, C. neoformans, H. capsulatum, Hantavirus, F. tularensis, Sandstorm exposure: Coccidioidomycosis, Bronchiectasis/CF: P. aeruginosa, P. cepacia, S. aureus. Community-acquired PNA in immunocompetent healthy adults: M. pneumoniae, C. pneumoniae, S. pneumoniae, H. influenzae. Elderly nursing home tenants: S. pneumoniae, H. influenzae, aerobic GN bacilli, anaerobes, Hospitalized ventilated patients: S. aureus, S. pneumoniae, P. aeruginosa, K. pneumoniae, Serratia spp, Enterobacter spp, E. coli, fungi. .
__% of adults are colonized with S. pneumoniae, and __% are colonized with M. catarrhalis.
5-10% of adults are colonized with S. pneumoniae, and 5% are colonized with M. catarrhalis.
What 2 bacteria are major causes of acute exacerbation in COPD patients?
H. influenzae and M. catarrhalis.
How can C. pneumoniae PNA be diagnosed?
The gold standard is culture, but this is not widely available. Commonly used serologic criteria used to evaluate C pneumoniae PNA are an IgM titer exceeding 1:16 or a 4-fold increase in the IgG titer by microimmunofluorescence (MIF). Serology is limited by a commonly delayed Ab response: the IgM Ab response may take as long as 6 weeks, and the IgG Ab response may take as long as 8 weeks to appear in primary infections.
What does the term “Legionellosis” mean?
Legionellosis refers to 2 distinct clinical syndromes: Legionnaires disease, which most often manifests as severe pneumonia accompanied by multisystemic disease, and Pontiac fever, which is an acute, febrile, self-limited, viral-like illness.
Which Legionella species and subgroups cause human disease most frequently in adults and children?
Although more than 70 Legionella serogroups have been identified among 50 species, L pneumophila causes most legionellosis. L pneumophila serogroup 1 alone is responsible for 70-90% of cases in adults. In a pediatric series, L pneumophila serogroup 1 accounted for only 48% of cases, serogroup 6 accounted for 33%, and the remaining cases involved other serotypes and species. Legionella micdadei and L dumoffii are the second and third most common species to cause Legionnaires disease in children, respectively,
What is the preferred means of laboratory diagnosis of SARS coronavirus?
While SARS-CoV appears to grow well in cell culture (Vero E6 cell lines), real-time PCR, performed on nasopharyngeal specimens, is the preferred means of laboratory diagnosis.
What bacteria cause native valve endocarditis (clinical picture is acute bacterial endocarditis)?
Most frequent is S. aureus. Less common causes include enterococci and certain streptococci, especially S. milleri.
What bacteria cause endocarditis of a previously abnormal native valve (clinical picture is subacute bacterial endocarditis)?
Viridans streptococci (S. sanguis, S. mutans, S. mitis), group B streptococci, group D streptococci (S. bovis), Enterococci (S. faecalis), and other HACEK organisms.
What bacteria cause infection of prosthetic heart valves?
Most common is S. epidermidis, followed by S. aureus. Cases arising a very long time after valve replacement tend to have a microbial DDx resembling that of subacute bacterial endocarditis.
What are the common underlying valve abnormalities seen in endocarditis affecting previously abnormal native valves (subacute bacterial endocarditis)?
In most cases, the basic valvular abnormality is due to rheumatic heart disease, most often affecting the mitral valve. Other cases are related to mitral valve prolapse, nodular dystrophic (age-related) calcification of the aortic valve, and congenital heart disease.
About 5-10% of cases of endocarditis are associated with negative blood cultures, the most common cause of which is prior antibiotic therapy. What are some other causes of blood culture-negative endocarditis (non-infectious and infectious)?
Non-infectious: Libman-Sacks endocarditis, nonbacterial thrombotic (marantic) endocarditis, carcinoid heart syndrome. Infectious: C. burnetii, Bartonella, Chlamydia, Legionella.
Bartonella species, especially B. ___ and B. ___, account for approximately 1% of all infective endocarditis cases and 10% of blood culture negative endocarditis.
Bartonella species, especially B. quintanta (associated with homelessness and chronic alcohol use) and B. henslae (associated with cat (kitten, usually) exposure), account for approximately 1% of all infective endocarditis cases and 10% of blood culture negative endocarditis.
What is the most useful confirmatory test for Bartonella endocarditis?
High titer (1:800) IgG has a high predictive value (IgM is usually gone by the time of presentation). Culture is difficult but should be attempted. PCR on blood or excised heart valves may be attempted.
What 2 organisms can cause endocarditis with little macroscopic (tend not to produce vegetations) or microscopic (sections may show only fibrosis, calcification, and a mononuclear infiltrate) findings?
C. burnetti and T. whipplei.
What are the most common causes of fungal endocarditis?
Candida spp > Aspergillus spp.
The histologic finding of follicular hyperplasia, monocytoid B-cell hyperplasia, and aggregates of epithelioid histiocytes in and around follicles is almost diagnostic of what infectious entity that can be seen in lymph node?
Toxoplasma.
In encephalitis the CSF can vary between normal and findings typical of viral meningitis (moderately increased protein, normal glucose), but the major exception is with what entity?
Herpes encephalitis, which can present with a bloody CSF, very high protein, and low glucose.
What are the most common viral causes of encephalitis?
HSV-1, arboviruses (St. Louis encephalitis, California encephalitis, West Nile virus, Western equine encephalitis, Eastern equine encephalitis), HHV-6, mumps virus, measles virus, and varicella-zoster virus.
What group of viruses is the most common cause of aseptic meningitis in all ages, causing up to 70% of cases?
The Enteroviruses (coxsackie A and B, echoviruses, poliovirus). Summer/fall outbreaks are typical.
The Enteroviruses (coxsackie A and B, echoviruses, poliovirus) are the most common cause of aseptic meningitis in all age groups, causing up to 70% of cases. What are other viral causes of aseptic meningitis?
HSV, mumps virus, HIV, LCMV (lymphocytic choriomeningitis virus).
What is lymphocytic choriomeningitis?
LCM is a rodent-borne viral infectious disease that presents as aseptic meningitis, encephalitis, or meningoencephalitis. Its causative agent is the lymphocytic choriomeningitis virus, a member of the family Arenaviridae. Although LCMV is most commonly recognized as causing neurological disease, as its name implies, infection without symptoms or mild febrile illnesses are common clinical manifestations. Additionally, pregnancy-related infection has been associated with congenital hydrocephalus, chorioretinitis, and mental retardation.
What is the preferred diagnostic test for acute lymphocytic choriomeningitis?
Acute lymphocytic choriomeningitis (LCM) can be diagnosed via detection of IgM antibodies by ELISA from serum or CSF. This is the preferred diagnostic test.
Traditionally, the list of most common agents causing bacterial meningitis was topped by H. influenzae type B. Why is it no longer at the top of the list?
Immunization has led to a major decline in H. flu meningitis (causes about 5% of cases now), and S. pneumoniae is now the most common agent (causes about 50% of cases now).
What are the most common causes of meningitis in neonates?
GBS, GN aerobic bacilli (E. coli, Klebsiellae), L. monocytogenes.
What are the most common causes of meningitis in infants and young children?
N. meningitidis, S. pneumoniae, H. influenzae type B.
What are the most common causes of meningitis in adults and elderly adults?
In adults, S. pneumoniae, followed by N. meningitidis. In elderly adults, S. pneumoniae, followed by L. monocytogenes, followed by GN aerobic bacilli.
HSV-1 encephalitis and HSV-2 meningitis are best diagnosed by what method on what specimen?
PCR on CSF.
___, the virus that causes exanthem subitum, is a common cause of viral encephalitis in children, and is thought to contribute to many cases of febrile seizures in children.
HHV-6, the virus that causes exanthem subitum, is a common cause of viral encephalitis in children, and is thought to contribute to many cases of febrile seizures in children.
What are arboviruses?
Arthropod-borne viruses, i.e., arboviruses, are viruses that are maintained in nature through biological transmission between susceptible vertebrate hosts by blood feeding arthropods (mosquitoes, psychodids, ceratopogonids, and ticks). Vertebrate infection occurs when the infected arthropod takes a blood meal. The term ‘arbovirus’ has no taxonomic significance. Arboviruses that cause human encephalitis are members of three virus families: the Togaviridae (genus Alphavirus), Flaviviridae, and Bunyaviridae. Some systems also include the virus family Reoviridae.
What are enteroviruses?
One of 17 (numbers vary) genera in the Picornaviridae family. This family is a large and diverse group of small RNA viruses characterized by a single positive-strand genomic RNA. The enterovirus genus is divided into 12 (numbers vary) species (Enterovirus A-H, Enterovirus J, Rhinovirus A-C) and there are numerous serotypes. But the important point is: The human enteroviruses include polioviruses, group A and B coxsackieviruses, echoviruses, enteroviruses, and rhinoviruses.
The mumps virus used to be the most common cause of winter/spring aseptic meningitis. Why is this no longer true, and what is the most common cause now?
Lymphocytic choriomeningitis virus is the most common cause of aseptic meningitis in winter/spring. The mumps virus used to be the most common cuase, but immunization has altered this pattern in the US.
