Sporadic vs variant CJD

Age of onset

Middle age to elderly

27 year



> 1 year


Rapidly progressive neurologic degeneration

Psychiatric symptoms



Rous sarcoma virus, HTLV I, HTLV II


Visna virus, HIV. Long incubation; immune suppression, hematopoietic system; CNS; arthritis. Host species specific. CPE in certain infected cells. Cone shaped nucleoid on TEM. Molecular characteristics: large genome; runcated gag gene; several processed gag proteins; polymorphism in envelope region; novel central orf separating the pol and env regions.


Foamy viruses


Enveloped, icosahedral, diploid +ssRNA. Group Specific Antigen (GAG). Replicates in nucleus. Classified A-D on TEM

Class A

Immature defective forms

Class B

Mature particle, eccentric nucleoid

Class C

Oncovirus C, centrally located core

Class D

Lentivirus, cigar shaped core




Sootey mangebe – west Africa.


Subtypes of virus. M major, A-J and O (outliers). Differ in aa content by at least 20%

HIV pathogenesis

Infection of cells w/ CD4 receptor via gp120 (T-helper, monocytes, dendritic cells). Activation of cells leads to destruction. Histiocytes infected but not destroyed. Infected cells bear the fusion protein (gp41). Multinucleated giant cells are formed and immune system is depressed. HR 1 and HR 2 are co-receptors for gp41. Direct killing of cell (TAT enhanced). Abberant production of cytokines and toxic factors which induce inflammation. Immune mediated destruction of virus infected or antigen coated cells. Direct or indirect action of non-structural regulatory genes. Various other indirect mechanisms (anergy, apoptosis, superantigen induced cells, proliferation and depletion of immune cells, defective signaling, molecular mimicry and autoimmunity). Provirus can integrate into host cell genome. Restriction/regulation of virus expression by cellular and viral factors (TAT). Mobility of viral infected monocytes and lymphocytes within host. Trapping and presentation of cell-free virus by follicular dendritic cells in nodes.

Retrovirus transmission

IV drugs, transfusion, sexual, in utero


T-cell leukemia in adults and tropical spastic paraparesis. Strains show 96-99% homology.


Hairy cell leukemia. Shares 65% homology w/ HTLV-1

HIV 1&2


Viral load

Circulating virus in seropositive patients. Viral load determined by HIV monitor test, RT-PCR. CD4/CD8 ratio useful for surveillance.

Clinical signs of AIDS

Anergy, skin test responses are absent, NK cell activity is reduced, polyclonal activation of B-cells, functional changes in T-cells, reduced response to mitogens, reduced IL2 and IFN gamma, aubacute dementia, kaposi's sarcoma seen in some patients. T-cells below 100. viral load better predictor than CD4 count. Fever, night sweats, fatigue, wasting syndrome (cachexia), chronic diarrhea (over 30 days). AIDS dementiac complex. Loss of concentration, depression, disorientation, opportunistic infections.


Fever, lymphadenopathy, pharyngitis, erythematous maculopapular rash, myalgia, or arthralgia, diarrhea, headache, nausea, vomitting, hepatosplenomegaly, thrush, weight loss, neurologic symptoms.

Opportunistic infections w/ AIDS

CMV, HSV, JCV-PML, EBV, mycobacteria, salmonella, Toxoplasma gondii, cryptosporidium, isospora, Pneumocysticarinii, Candida albicans, Cryptococcus neoformans, histoplasmosis, Coccidioides, Kaposi's Sarcoma, B-cell lymphoma.

HIV diagnosis

Detection of Ab by EIA screening test (high sens, low spec), western blot (detect Ab against HIV envelope and core proteins. 60-90% crossreactivity w/ HIV-2). Detection of core p24 antigen by PCR

Congenital infection

Hematogenous. Infection of placenta. Repeated testing needed to confirm infection. Neonate fails to reach developmental milestones, decreased cognitive skills, weight loss, opportunistic infections. AZT for mothers. For newborns, testing needs to be done repeatedly because maternal antibodies may be present.

Treatment of HIV

, , combination therapy

HIV therapy

Nucleoside-analog reverse transcriptase inhibitors NRTIs (AZT, ddl, ddC, d4t, 3tc), Non-nucleoside reverse transcriptase inhibitors (protease inhibitors) NNRTIs (nevirapine, delavridine), combination therapy

HTLV-1 epidemiology

Endemic in Japan, Taiwan, West Indies, South America, Central America, Central Africa.. generally occurs during the perinatal period, w/ seropositive rate increasing subsequently. Mostly females.

HTLV-1 screening

ELIA, agglutination method, Western blot technique, ATL, provirus may be detected by PCR.

HTLV diagnosis

Screening tests can be conducted by ELISA or an agglutination method. Western blot. To confirm ATL, detection of virus in leukemic cells may be done by PCR


Bacillus anthracis

Only Gram positve zoonoses. Rod. Bioweapon. Heat resistant central endospores. Non-hemolytic. Produces capsule. Glutamyl polypeptide: amount of capsule correlates directly w/ virulence. Found in hoofed animals (horses, cattle).

Lethal factor

Causes necrosis of tissues

Edema factor

Causes infiltration and tissue swelling: may enhance distribution of lethal factor

Protective antigen

Probably same substance as edema factor, but w/ this added effect

Cutaneous anthrax

The most common in humans, least life-threatening. Begins as a papule. Progresses to eschar. Edema, redness, and/or necrosis w/o ulceration may occur. Form most commonly found in natural cases. Incubation period of one to two days. 20% fatality w/o treatment.

Gastrointestinal anthrax

Rare in humans, most common in grazing animals. High mortality. Abdominal distress. Bloody vomiting or diarrhea, followed by signs of septicemia. GI illness sometimes seen as oropharyngeal ulcerations w/ cervical adenopathy and fever. Develops after ingestion of contaminated or poorly cooked meat. Incubation of 1-7 days. 25-60% fatality.

Pulmonary anthrax

Highest mortality in humans. Rare under natural circumstances: “Wool-Sorter's disease”. Flu-like. Myalgia, fatigue, fever, w/ or w/o respiratory symptoms followed by hypoxia and dyspnea. Often radiographical evidence of mediastinal widening. Meningitis in 50% of patients. Rhinorrhea (rare). 97% death w/o treatment and 75% w/ treatment.


Black necrotic ulcer seen with cutaneous anthrax at original lesion.

Cut. Anthrax diagnosis

Gram stain. PCR, culture of vesicle fluid, exudate, or eschar material. Blood culture if systemic symptoms present. Biopsy for immunohistochemistry, especially if person is taking antimicrobials

Inhalation anthrax diagnosis

Chest X-ray, biopsy for immunohistochemistry, Gram stain, PCR, or culture from normally sterile area, pleural fluid block for immunohistochemistry

Chest X-ray in. anthrax

Widened media stinum, pleural effustions, infiltrates, pulmonary congestion

Brucella species reservoir

Venereal disease of farm animals. People w/ contact to animals at risk.

Brucella species control

Pasteurization of milk.

Brucella species pathogenesis

Penetrates skin or mucous membrane. PMNs carry to lymphatics. Multiplication in macrophages. Humoral immunity has no effect. Failure of T-cell response results in granulomatous sites of bacterial multiplication within the RES. Waves of bacteria are released into the circulation from within these sites resulting in recurrent bacteremia.

Brucellosis clinical findings

Onset: drenching sweat w/ high fever in afternoon or evening. Chronic periods of nocturnal fever may persist for months to years. Prolonged cases result in marked weight loss. Few other physical findings or signs. Sometimes glandular or hepatic symptoms.

Brucellosis diagnosis

Serodiagnosis is not definative. Agglutination of heat killed Brucella sp. Cells (1:640 rise in titer in acute disease). Isolation and culture: definiative. Specimen: blood, lymph node, bone marrow, liver. Special considerations: must incubate in CO2. For B. abortus. Blood agar is OK. Prolonged incubation (2-4 weeks) sometimes needed for blood cultures.

Brucellosis therapy

Chemotherapy does not get rapid results. Fever may remain upto 7 days after treatment has begun. Treatment must be prolonged and relapses are common for up to 3 months. Tetracycline. Streptomycin, rifamycin, gentamycin are secondary. No vaccine for humans

Francisiella turarensis

Gram negative coccobaccilus. Facultative. Nutritionally fastidious. Will not grow on normal culture; requires supplemental sufhydral compounds. Grown on cysteine-glucose blood agar (aerobic). Requires 2 to 10 days for visible growth.

F. tularensis epidemiology

Small wild mammals (rabbits, squirels, muskrats, beavers, deer). Ticks and deer flies are vectors to both animals and man. naturally in the Southwest to central US.

F. tularensis pathogenesis

Entry through inhalation, ingestion, or injection. Minimum infectious dose of 100 cells. Bacteremic spread infects RES with eventual granuloma formation. Ulcerated lestions develop at injection site. Recovery confers long lasting immunity.

F. tularensis clinical presentation

Incubation 2-5 days. Acute onset of fever, chills, and malaise. Various forms depending on site of infection (ulcero-glandular (from injection: least mortality) typhoidal (resulting from ingestion), pneumonia from inhalation (greatest mortality). All progress to systemic infection w/ mortality of 5-30%

F. tularensis diagnosis

Difficult because disease is rarely suspected. Careful history. Culture is risky and difficult for lab personnel. Direct fluorescent antibody on appropriate clinical material is sufficient. Serodiagnosis: rise in agglutinating antibodies 1:40 to 1:320 in 1 to 2 weeks. Treatment is streptomycin

Pasteurella multicoda

Gram negative coccobacillus. Facultative, oxidase positive, grows readily on enriched medium like blood agar, but not on media selective for Gram negatives. Local infection at site of inoculation. Diffuse cellulitis w/ clear border. Systemic infection very rare. Normal respiratory flora of many lower animals, including cats and dogs. Human is infected by bite or scratch. Sometimes found in human sputum. Diagnosis from culture of aspirated pus. Treatment: penicillin

Burkholderia mallei

(Pseudomonas mallei). Causes glanders. Contracted from domestic animals (horses, donkeys, mules). Asia, middle east, africa, central and soutth america. No free living state. No man-to-man transmission.

Burkholderia pseudomallei

(Pseudomonas pseudomallei). Causes melioidosis (Whitmore's diseasee). Free living in stagnant waters. Endemic in Southeast asia. Scattered cases elsewhere. Infects sheep, cattle, pigs, cats as well as humans. Man to man transmission rare but possible

Glanders and melioidosis symptoms

Acute local infection (ulcer at original site, can spread to lympatics). Pulmonary infection. Acute septicemia (chronic illness predisposes. Highest fatality). Chronic visceral damage: multiple abscesses

Glanders and melioidosis diagnosis

Resembles TB. Resembles many other infections. Isolation of bacteria from blood, sputum, urine, skin lesions. No rapid diagnosis available

Glanders and melioidosis prognosis

Chronic infection can lay dormant for 10 to 20 years. Complication of HIV and diabetes. All forms can progress to septicemia. Septicemia 95% mortality untreated; 35-60% mortality w/ treatment.

Yersinia pestis

Enterobacteriacae. G-, non-spore forming, rod, oxidase-, facultative, glucose fermented. Grows readily in standard enteric media. Polysaccharide capsule in virulent strains.

Yersinia pestis reservoir

Voles, rats, ground hogs, rock squirrels. Establishes itself in a balance w/ the population (fatal in rats as well). Semi-arid regions of southwest USA (four corner states) and Southeast Asia.

Xenophsilla cheopis

The rat flea. Main vector. Organism blocks GI tract of flea, when it takes a blood meal, it will regurgitate bacteria into new host.

Yersinia pestis pathogenesis

Flea bites, organism gets to lymph nodes, higher temperature induces formation of virulence factors, rapid multiplication, rapid swelling of infected lymph nodes. Progresses to bacteremia, which seeds liver, spleen, lungs, and sometimes meninges. Pulmonary transmission may then occur via respiratory droplets.

Yersinia pestis Clinical symptoms of bubonic

Incubation: bubonic form: 4 to 7 days. Swollen inguinal lymph nodes, increasing fever, pooling of blood and microhemorrhages in face and extermities.

Yersinia pestis Clinical symptoms of pneumonic

18 to 36 hour incubation. Vilent and fulmonating bacterial pneumonia. Nearly always fatal.

Diagnosis of bubonic plague

Case history. lymph node aspirate or blood sample. Fluorescent antibody. Rapid etiologic diagnosis. Culture dangerous and rarely done.

Diagnosis of pneumonic plague

Case history. Sputum examination, fluorescent antibody rapid etiologic diagnosis. Insufficient time for culture.

Yersinia pestis treatment


Borellia recurentis vector

Louse tick or tick borne transmissibility.

B. burgorferi vector

Transmitted by Ixodes sp. Ticks. Ticks must be removed by the head as crushing the abdomen may result in contents being forced into the blood. Northern hemisphere temperate zones 30-50 degrees, southern hemisphere has few cases in the same latitude range.

Borrelia sp.

Grough, loose gram: spiral. Outer membrane proteins encoded by plasmids increasing antigenic variability. Can grow in axenic artificial liquid cultures (barbour-Stoenner-Kelly medium)

B. recurentis symptoms

3-4 day incubation. Abrupt onset of chills and fever. Organism can invade the spleen, liver, kidneys, eyes or brain from blood. Cycles of attack each shorter and less severe than the first

B. recurentis diagnosis

Stained blood smear

B. recurentis treatment

Tetracycline or chloramphenicol

B. burgorferi life in tick

Adheres to epithelial cells of ticks midgut and remains there indefinately in quasi-dormant state. Upon sensing avian/mammalian blood, it becomes activated and moves to the ticks salivary gland for injection.

Ixodes life cycle

2 years. Eggs -spring-> larvae -fall have blood meal-> nymphs -winter-> dormant -spring/summer blood meal-> adults -fall-> mate/lay eggs

Primary lyme disease stage

Erythema chronicum migrans (Target lesion). Reddening and swelling at sites other then the site of the tick bite.

Secondary lyme disease stage

Annular skin lesion (exanthem), CNS, cardiovascular, opthalmic and musculoskeletal manifestations.

Tertiary lyme disease stage

Residual organisms in protected niches give rise to ACA acrodermatitis chronicum atrophicans or intermittent chronic arthritis, chronic encephalopathym polyneuropathy, leukoencephalitis, chronic cardiomyopathy

Lyme disease spread to blood

Can occur immediately after infection. Meningitis, carditis, musculoskeletal pain, eye abnormalities

Lyme disease diagnosis

Blood smear and spot B. burgdorferi. Serology for later stage is unreliable: ELISA, IFA

Lyme disease treatment

Doxacycline or amoxacillin for early. For late, ceftriaxone or cefotaxine for prolonged period of time. Vaccine is made of B. burgderferi outer surface protein (Osp). Various osp types (A, B, C) are known. High levels of Anti OspA IgG are formed in blood vaccinated persons. LYMErix is current vaccine in states (recombinant L-OspA with adjuvant).

Leptospira interrogans

Direct contact or water borne transmission. Spirochete. Kindey's of many wild animals. Man is an accidental host. Gram-, spiral, hooked end, motile, sensitive to heat, drying, and most chemicals. Survives well in slightly alkaline ground water or soil. Enters host through skin/mucus membranes. 172 subtypes based on cell surface antigens. subtypes may be host specific.

Leptospirosis symptoms

8 to 12 days. Chlls, headache, severe muscle pain, especially in thighs, calves and abdomen. Later symptoms include infectious jaundice (Weil's disease), renal dysfunction, severe hemorrhagic manifestations. High mortality rate

Leptospirosis diagnosis

Serodiagnosis: macro or micro agglutination. Culture can take two months. Not practical.

Leptospirosis treatment

Penicillin, tetracycline, or cephalosporin