spirochetes Flashcards
1
Q
what is the taxonomy of spirochetes?
A
Phylum spirochaetes, class spirochaetia, order spirochaetales
2
Q
spirochetes are motile or immotile?
A
Spirochaetes are motile (i.e. they can move) by means of flagellae located in the periplasmic space (i.e. between the outer and inner membranes). These flagellae are also known as axial fibrils.
3
Q
what is the periplasm?
A
- Space between the outer membrane and the cytoplasmic membrane
- Only present in gram-negative organisms
- Contain peptidoglycan and beta-lactamase
- Contains components exiting the bacteria such as hydrolytic e
4
Q
what are flagella?
A
- filamentous organelles that aid in the movement of bacteria
- Peritrichous flagella: flagella around the bacterium (e.g., Escherichia coli)
- Lophotrichous flagella: several flagella at one pole (e.g., Pseudomonas)
- Polar flagella: one flagellum at one of the bacterial poles (e.g., Vibrio cholerae)
5
Q
name important spirochetes and associated diseases
A
- Treponema pallidum-syphilis
- Treponema pallidum endemicum-Bejel
- Treponema pallidum pertenue-Yaws
- Treponema carateum-Pinta
- Borrelia Burgdorferi-Lyme disease
- Borrelia recurrentis-Louse born relapsing fever
- other Borrelia spp-tick-borne relapsing fever
- Leptospira Interrogans-Leptospirosis
6
Q
spirochetes can be diagnosed by staying with Gram stain. True/False
A
False.
The bacteria are difficult to visualize under light microscopy due to their small diameter.
7
Q
what microscopy is used to diagnose spirochetes?
A
A microscopy technique that illuminates specimens against a dark background. It can be used to visualized spirochetes such as Treponema pallidum.
8
Q
serology is unsless in spirochetal disease diagnostics. True/False.
A
False.
It is the major diagnostic technique
9
Q
culture is useless to diagnose spirochetal diseases. True/False.
A
True
Treponema pallidum won’t grow in the laboratory & Leptospira interrogans and Borrelia burgdorferi only grow on specialized culture media
10
Q
does PCR is used to diagnose spirochetal diseases
A
Yes
11
Q
what treponemal species responsible for human disease?
A
T. pallidum, T. carateum, Treponema Vincenti
12
Q
what are endemic treponemal diseases
A
- Yaws, endemic syphilis (bejel), and pinta collectively constitute the endemic treponematoses
- Not sexually transmitted
- Yaws is the most common worldwide; characterized by skin and bony lesions
13
Q
All Treponema organisms look the same on microscopy and elicit similar serological responses. True/False
A
True
i.e. it’s not possible to tell the difference between them based on lab tests
14
Q
how different Treponemal diseases are distinguished?
A
The diseases are distinguished on the basis of epidemiological & clinical features.
15
Q
what are the epidemiological features of Yaws, Pinta, and Bejel?
A
- -Yaws has a widespread distribution in developing countries esp. in Central Africa/Asia; affects skin and bones
- -Bejel occurs mainly in the Sahel region in sub-Saharan Africa and affects skin and bones
- -Pinta occurs in Central America
16
Q
define the Yaws
A
Yaws is a poverty-related chronic skin disease that affects mainly children below 15 years of age (with a peak between 6 and 10 years).
It is caused by the bacterium - is a Treponema pallidum subspecies pertenue and transmitted by skin contact. Yaws mainly affects the skin, but can also involve the bone and cartilage.
17
Q
T. Pallidum can affect also animals. True/False
A
False.
It is Obligate human pathogen
18
Q
T. pallidum is a highly invasive and persistent pathogen in the human host.True/False
A
True
19
Q
what is the second most common route of syphilis spread?
A
Trans-placental spread is the second most common route (congenital syphilis)
20
Q
syphilis mostly occur in developed countries. True/False
A
Most cases occur in low & middle-income countries
21
Q
what is the risk of acquisition of syphilis from a single sexual contact with an infected person
A
30%
22
Q
what increases the risk of transmitting or acquiring syphilis?
A
active genital lesion
23
Q
Spirochaetes cannot survive on dry skin surfaces. True/False
A
True
24
Q
Syphilis can be transmitted via oral sex. True/False
A
True
50% of cases in a recent London outbreak in MSM
25
how transmission of syphilis occurs?
Transmission- contact with lesions (chancre or condylomata lata/ mucous patches) containing organisms
26
what are other rare routes of syphilis acquisition?
rarely occur via blood transfusion, needle stick injury, needle-sharing
27
in which stages syphilis is infectious?
“Early infectious syphilis“ = Primary, secondary and early latent.
28
transmission of syphilis in developed vs developing countries?
mainly homosexual vs heterosexual
29
what are the risks of syphilis during pregnancy?
- Syphilis during pregnancy is a major cause of stillbirth and congenital infection worldwide.
- Preventing congenital syphilis by eliminating mother-to-child transmission of syphilis is a priority for the WHO.
30
describe the pathophysiology of syphilis
Spirochetes invade the body → disseminate systemically within hours → bind to endothelial cells → inflammatory reaction → endarteritis and perivascular inflammatory infiltrate
31
how TreponemaPallidum crosses the blood vessels
passes between tight junctions
32
how Treponema evade host immune response?
Structure of outer membrane “hides” the spirochaete from the host immune response
Outer membrane lacks lipopolysaccharide and expresses very few proteins on its surface so it is not very antigenic and thus helps the organism “hide” from the host’s immune response- “the stealth pathogen”.
33
what is the primary chancre?
Site where the treponemes entered the body, causing obliterating endarteritis. The lesion is painless, due to the ischemic death of sensory vasa nervorum.
34
how treponema enter the body?
Enters the body through small breaches in genital/ anorectal/ oropharyngeal mucosa
35
what is secondary syphilis?
Secondary syphilis is the manifestation of dissemination through the bloodstream. Motility helps it disseminate and also to penetrate between tight junctions.
36
what ar the virulence factors of Treponema?
Virulence factors include outer membrane proteins that promote adherence of lymphocytes/monocytes to host vascular cells.
37
Treponemas spread through the bloodstream and lymphatic system.True/False
True
38
Treponemas can cause endarteritis. True/False
True
| It can be obliterating if reactive endothelial hyperproliferation occurs and results in ischemia and necrosis.
39
what is the reason of perivascular inflammatory infiltrate seen with treponema infection?
perivascular inflammatory infiltrate
40
how much is the incubation period of syphilis?
10–90 days; on average 21 days
41
what is the window period?
The duration of time between the onset of infection and the point at which a laboratory test can detect the infection.
42
if a patient with a history of the unprotected sexual encounter last week tests negative for syphilis this week, what you should do?
If there is a significant risk of syphilis, needs to have serology repeated 3 months after exposure risk.
43
describe the clinical features of primary syphilis
1) Primary lesion (chancre)
- -Typically starts out as a solitary, raised papule (usually on the genitals)
- -Evolves into a painless, firm ulcer with indurated borders and smooth base
- -Resolves spontaneously within 3–6 weeks, typically without scarring
2) Regional (usually inguinal) nontender lymphadenopathy
44
how long does it take of primary chancre to resolve?
3–6 weeks
45
does lymphadenopathy that is seen in primary syphilis painfull?
No
| Regional (usually inguinal) nontender lymphadenopathy
46
the chancre is painfull. True/False
False.
| painless, firm ulcer with indurated borders and smooth base
47
describe the evolution of the chancre
Starts as a papule; the papule erodes to form a painless ulcer with raised borders – a chancre
48
lymphadenopathy occurs with the appearance of the chancre. True/False.
False
| 1-2 weeks after the chancre appearance
49
chancre needs to be treated to go away.True/False.
False.
The chancre usually lasts 3-6 weeks, then goes away without treatment
However, the infection has not gone away
50
what is the most common location of chancre in females?
in women the primary chancre often occurs on the cervix so is not visible externally
51
do chancres occur erxtragentially?
yes
| mouth, rectum, etc
52
when secondary syphilis occurs?
Begins approx. 8–12 weeks after primary infection; typically lasts 2–6 weeks, represent a systemic spread of the spirochetes, inducing an immunologic reaction
53
what are the clinical features of secondary syphilis?
1) Constitutional symptoms
- -Generalized nontender lymphadenopathy
- -Fever, fatigue, myalgia, headache
2) Specific features
- -Polymorphic rash
a) Typically nonpruritic macular or papular rash
b) Disseminated; involves trunk and extremities, also the palms and soles
c) Reddish-brown or copper-colored
d) Heals within 6 months, but may recur
- -Condylomata lata
a) Broad-based, wart-like papular erosions
b) Located in the anogenital region, intertriginous folds, and on oral mucosa
- -Additional lesions
a) Patchy alopecia (moth-eaten alopecia)
b) Sore throat (acute syphilitic tonsillitis)
c) Splenomegaly
d) Generalised lymphadenopathy in about 50%
e) CNS involvement in 40%: aseptic meningitis, cranial nerve palsies
f) Other organ/tissue involvement e.g., uveitis, periostitis, joint effusions, glomerulonephritis, hepatitis
54
when a rash of secondary syphilis occurs?
occurs 3-4 days after the flu-like illness of secondary syphilis.
The rash is widespread but characteristically includes palms of the hands & soles of the feet.
55
what is the characteristic location of the rash of secondary syphilis?
palms and soles
56
what is the condylomata lata?
Condylomata lata, mucous patches- skin/ mucosal lesions which are very infectious
57
what are the additional features of secondary syphilis?
- Splenomegaly
- Generalised lymphadenopathy in about 50%
- CNS involvement in 40%: aseptic meningitis, cranial nerve palsies
- Other organ/tissue involvement e.g., uveitis, periostitis, joint effusions, glomerulonephritis, hepatitis
58
what is the outcome of secondary syphilis?
The signs and symptoms of secondary syphilis resolve slowly over weeks to months.
The infection may resolve spontaneously at this point or it may progress to the latent (clinically inactive) stage of the disease
59
what is latent syphilis?
- -No clinical symptoms, despite seropositivity
- -May last months, years, or even for the entire life of the patient
- -Disease may resolve, reactivate, or progress to tertiary syphilis
60
what are the clinical symptoms of latent syphilis?
no symptoms
61
what are the stages of latent syphilis?
- -''Early” latent syphilis (the 1-year period after the resolution of the lesions of secondary syphilis)
- -“Late” latent syphilis (>1 year after secondary syphilis)
62
in what stage of latent syphilis the patient is infectious?
early latent
| Recurrence of infectious secondary syphilis lesions often occurs during the early latent period
63
what are the characteristics of tertiary syphilis?
1) Gumma: destructive granulomatous lesions with a necrotic center that tend to ulcerate
- -May affect any organ, e.g., skin, internal organs, bones
2) Cardiovascular syphilis: aortitis, ascending aortic aneurysm (thoracic aortic aneurysm), syphilitic mesaortitis, aortic root dilation
- -Due to Treponema-induced aortitis of the vasa vasorum of the large vessels (esp. the aorta), resulting in aneurysm formation
3) Neurosyphilis
- -Asymptomatic neurosyphilis: documented CNS invasion without clinical signs or symptoms
- -Symptomatic neurosyphilis
* Acute meningeal syphilis: symptoms of acute meningitis
* Meningovascular syphilis: subacute stroke, cranial neuropathies
* Late (parenchymal) neurosyphilis
1) General paresis
2) (Frontotemporal) dementia, psychosis, cognitive dysfunction, and personality changes
3) Argyll Robertson pupil: bilateral miosis; pupils accommodate, but do not react to direct or indirect light
4) Tabes dorsalis (syphilitic myelopathy): demyelination of the dorsal columns and the dorsal root ganglia; occurs approx. 25–30 years after infection
5) Broad-based ataxia
6) Dysesthesias
- --Loss of sensation, predominantly in the lower extremities
- --Sharp, shooting pain in the legs and the abdomen
64
what is the probability of tertiary syphilis after untreated secondary syphilis?
Tertiary syphilis is thought to occur in approximately 1/3 of untreated cases.
**Note this is the clinical course of UNTREATED syphilis; if the patient is diagnosed and treated with penicillin at any stage, the infection will be cured and progression will not occur.
65
tertiary syphilis is easy to diagnose clinically. True/False
False.
| Difficult to detect clinically as it may occur many years after the initial infection
66
what are the presentations of neurosyphilis?
1) Neurosyphilis includes chronic meningitis, stroke, tabes dorsalis (occurs in 1 in 6 untreated cases, usually more than 5 years after initial infection). Increased incidence in patients with HIV. Pathology: lymphocytic infiltrates.
2) “General paresis of the insane”- progressive dementia thought to have accounted for 10% of psychiatric hospital admissions in the pre-antibiotic era. Rare nowadays.
3) Cardiovascular syphilis: myocarditis/conduction abnormalities, aneurysm (10- 40 years after initial infection). Pathology: endarteritis obliterans of vasa vasorum
67
what is the reason of thoracic aortic aneurysm seen in tertiary syphilis
endarteritis obliterans of vasa vasorum leading to the decreased blood supply to the aorta
68
infiltrate that is seen in tertiary syphilis is composed of...
lymphocytes, plasma cells (characteristic !!!)
69
what is the gumma?
- -destructive granulomatous lesions with a necrotic center that tend to ulcerate, an example of perivascular inflammatory infiltrate; consists mainly of monocytes
- granulation tissue
70
what are the ways of acquisition of congenital syphilis?
--Fetus: transplacental transmission from infected mother
Increased risk of transmission with recent syphilis infection
Risk of transmission increases with gestational age
--Neonate: perinatal transmission during birth
71
what are the clinical features of congenital syphilis?
1) Early congenital syphilis (onset < 2 years of age)
- -Hepatomegaly and jaundice
- -Rhinorrhea with white or bloody nasal discharge
- -Maculopapular rash on palms and soles
- -Skeletal abnormalities (e.g., metaphyseal dystrophy, periostitis)
- -Generalized lymphadenopathy (nontender)
2) Late congenital syphilis (onset > 2 years of age)
- -Typical facial features: saddle nose, frontal bossing, short maxilla
- -Dental findings: Hutchinson's teeth (notched, widely spaced teeth); mulberry molars (poorly developed first molars)
- -Eyes and ears: interstitial keratitis, sensorineural hearing loss
- -Skin: rhagades (perioral fissures), gummas
- -Skeletal: saber shins (anterior bowing of the tibia), painless arthritis in knees and other joints
- -Neurological: cranial nerve palsies (e.g., CN VIII defect causing deafness), intellectual disability, hydrocephalus
72
The majority of newborns with congenital syphilis are asymptomatic and go on to develop symptoms in the first few months following birth. True/False
True
73
is there a risk of stillbirth due to syphilis in pregnancy?
Approx. 25% risk of stillbirth
| Death can also occur after delivery
74
what is the prevention of congenital syphilis?
Screening (serology)- routine for all pregnant women in Ireland
If positive, treat the mother with IM penicillin
75
all pregnants need to be screened for syphilis. True/False
True
76
what is the management of congenital syphilis?
--Infant assessed clinically
--Serology +/- x-rays and lumbar puncture if clinical suspicion of syphilis
--Management (if confirmed congenital syphilis)
10 days penicillin IV/ IM
77
can we treat syphilis during pregnancy with penicillin?
Yes
78
who should be tested for syphilis?
Symptomatic patients
- -Asymptomatic patients (screening)
- -Patients at genito-urinary medicine (GUM) clinic/ patients presenting with other sexually-transmitted infections (STIs)
- -Antenatal patients (pregnants)
- -Blood donors
79
list diagnostic methods for syphilis
1) serological testing
- treponemal test
- nontreponemal test
2) direct detection of the pathogen
- -Darkfield microscopy, may be combined with immunofluorescence
- -Polymerase chain reaction (PCR
80
what are the principles of a treponemal test?
- -Indication: confirmatory test after a positive or equivocal nontreponemal test (high positive predictive value)
- -Interpretation: positive results indicate active syphilis or persistent antibodies from a prior infection
- -Commonly used tests
1) Treponema pallidum particle agglutination (TPPA)
2) Fluorescent treponemal antibody absorption test (FTA-ABS)
81
name 1 most commonly used treponemal test
FTA-ABS
82
what are the principles of nontreponemal tests?
- -Indications: screening, evaluation of disease activity , monitoring response to treatment
- -Commonly used tests
1) Rapid Plasma Reagin (RPR): generally the test of choice
2) Venereal Disease Research Laboratory (VDRL)
- Especially useful in the evaluation of neurologic involvement using cerebrospinal fluid.
- Many false-positive results due to cross-reacting antibodies in pregnancy, viral infections (e.g., EBV), rheumatic fever, lupus, or leprosy
83
what are the 2 most commonly used nontreponemal tests?
RPR and VDRL
84
what are the indications fo nontreponemal tests?
screening, evaluation of disease activity, monitoring response to treatment
85
what are the indications for treponemal tests?
confirmatory test after a positive or equivocal nontreponemal test (high positive predictive value)
86
what conditions yield false-positive results with nontreponemal tests?
Many false-positive results due to cross-reacting antibodies in pregnancy, viral infections (e.g., EBV), rheumatic fever, lupus, or leprosy
87
what is detected by nontreponemal tests?
Detect nonspecific anti-cardiolipin antibodies; sensitive, but not specific! (vs treponemal test detect specific antibodies against treponema)
88
what are the indications of tests used to directly detect pathogen?
definite tests to detect primary and secondary syphilis when a specimen can be obtained (e.g., exudative chancre, condyloma)
89
what test for direct pathogen identifying you know?
- -Darkfield microscopy, may be combined with immunofluorescence
- -Polymerase chain reaction (PCR)
90
what is the difference between treponemal and nontreponemal tests?
1) Treponemal tests e.g: These antibody titres rise during active infection and remain high even after syphilis has been treated and cured.
2) Non-treponemal tests e.g. RPR: These antibody titres rise in active infection but fall after treatment and may disappear altogether.
91
which test is useful to detect relapse and reinfection?
1) treponemal
2) nontreponemal
nontreponemal
92
what is test is used to monitor response to treatment?
nontreponemal tests
93
which test is used initially to diagnose syphilis
the nontreponemal test then confirmed by a treponemal test
94
If RPR negative & TPPA positive suggest?
past infection
95
what is the prozone phenomenon?
RPR can be false negative because of prozone phenomenon i.e. very high concentration of antibodies in serum, which stops the formation and precipitation of antigen-antibody complexes required to see a positive result. The prozone phenomenon can be overcome by diluting the serum.
96
what you should do to avoid the prozone phenomenon?
dilute the serum
97
what can be the reason of the false-positive result of the treponemal test?
Remember that endemic treponemal diseases (e.g. yaws) can’t be distinguished from syphilis in the lab; positive serology may reflect current or previous infection with one of these diseases in a patient from an endemic area.
98
do you need to repeat the negative test in -risk group?
no
99
do you need to repeat the test in high-risk group if there is a high clinical suspicion?
yes
100
how dark-field microscopy and PCR are carried out?
1) Dark-field: on a fluid sample from an active lesion within 10 minutes after collection (while the spirochaetes are still alive and actively motile)
2) PCR: of exudate from chancre: more sensitive than dark field microscopy but not commercially available
101
what is the treatment of choice of primary syphilis?
benzathine penicillin G
- -Primary, secondary, or early latent: IM, a single dose is sufficient
- -Late latent, tertiary, or date of transmission unknown: weekly IM injections over a 3-week course
- -Neurosyphilis: IV for 10–14 days
102
if the patient is allergic to penicillin, what are the other treatment options?
- -Treat with doxycycline or ceftriaxone
- -In neurosyphilis: desensitization and treat with penicillin
- -During pregnancy: desensitize and treat with penicillin
103
if a pregnant patient with syphilis is allergic to penicillin, what you should do?
desensitize and treat with penicillin
104
if a patient with neurosyphilis is allergic to penicillin, what you should do?
desensitize and treat with penicillin
105
what is Jarisch-Herxheimer reaction?
1) acute, transient, systemic reaction to bacterial endotoxins and pyrogens that are released after the initiation of antibiotic therapy
2) Epidemiology: Commonly seen during the treatment of infections with spirochetes (Borrelia, Leptospira). In syphilis, the Jarisch-Herxheimer reaction is most often seen if treatment begins in the early phases of the secondary stage.
3) Clinical features
- -Flu-like symptoms: fever, chills, headache, myalgia
- -Accompanied by tachypnea, hypotension, and tachycardia
- -Syphilitic exanthema may flare-up
- -Usually self-limiting within 12–24 hours
4) Treatment
- -NSAIDs for symptomatic treatment
106
what is the prevention of syphilis?
- -Condoms prevent transmission of syphilis and other STDs.
- -Syphilis is a nationally notifiable disease.
- -No vaccine available
- -Antenatal screening and treatment of mothers with positive serology (to prevent congenital syphilis
107
what is the treatment for Jarisch-Herxheimer reaction
NSAIDs and symptomatic treatment
108
what is the best way to prevent syphilis in pregnancy
Antenatal screening and treatment of mothers with positive serology (to prevent congenital syphilis
109
what is Lyme disease?
Lyme disease (or borreliosis) is a tick-borne infection caused by certain species of the Borrelia genus (B. burgdorferi in the US), a genus of facultative intracellular bacteria. There are three stages of Lyme disease. Stage I (early localized disease) is characterized by erythema migrans (EM), an expanding circular red rash at the site of the tick bite, and may be associated with flu‑like symptoms. In stage II (early disseminated disease), patients may present with neurological symptoms (e.g., facial palsy), migratory arthralgia, and cardiac manifestations (e.g., myocarditis). Stage III (late disease) is characterized by chronic arthritis and CNS involvement (late neuroborreliosis) with possible progressive encephalomyelitis. Lyme disease is a clinical diagnosis in patients presenting with EM. Serological tests (e.g., Western blot; enzyme-linked immunosorbent assay) can help support the clinical diagnosis, especially if the presence of EM is not known or questionable. Lyme disease is treated with antibiotics; the drugs of choice are doxycycline for localized disease and ceftriaxone for disseminated disease.
110
what is the cause of Lyme disease?
Borrelia Burgdorferi
111
what is the reservoir of Lyme disease?
Rodents, birds
112
what is the vector of Lyme disease?
Ixodes scapularis (deer or black-legged tick)
113
list disease except Lyme caused by Borrelia species
1) louse-borne relapsing fever
| 2) tick-borne relapsing fever
114
what is the cause of louse-borne relapsing fever?
Borrelia recurrentis
115
what are the reservoirs fo Louse borne relapsing fever vs tick-borne relapsing fever?
humans vs rodents
116
what is the epidemiology of louse-borne relapsing fever?
This is very uncommon in most countries. Body lice are associated with very crowded living conditions and poor hygiene e.g. as found in refugee camps. B. recurrentis infections are rarely encountered outside the Horn of Africa (Somalia/ Eritrea/ Ethiopia) but a number of cases were identified in Europe in 2015/ 2016 in migrants recently arrived from these countries.
117
what is the epidemiology of Lyme disease?
- -Incidence: most commonly reported vector-borne disease in the US
- -Geographical distribution: primarily the Northeast and upper Midwest
118
Borrelia Burgdorferi is a zoonosis. true/False
True
119
Deers are thought to be a reservoir for Lyme disease. True/False
Deer are not thought to be reservoirs for Lyme disease but they do sustain tick populations as they are a source of blood meals for the ticks.
120
how tick transmits the infection?
Infection is transmitted through tick saliva
121
how much the tick needs to be attached to the skin to transmit the infection?
It requires between 36 and 48 hours of attachment for the bacteria that causes Lyme to travel from within the tick into its saliva
122
Lyincidence of Lyme is highest in what season?
May-August
123
what are the vectors of Lyme disease transmission in Europe vs the USA?
Ixodes ricinus is the vector in Europe; Ixodes scapularis is the major vector in the USA
124
what are the clinical features of stage 1 Lyme disease?
1) Symptoms develop within 7–14 days after a tick bite.
2) Erythema chronicum migrans (EM)
- -Occurs in 80% of infected individuals
- -Usually a circular, slowly expanding red ring around the bite site with central clearing
- -Typically warm, painless
- -EM is often the only symptom.
- -Self-limiting (typically subsides within 3–4 weeks)
3) Flu‑like symptoms
125
what is the pathophysiology of erythema migrans?
The erythema is not caused by an allergic reaction, but by an immunologic reaction from the bacteria spreading locally in the dermis. After proliferating in the dermis, bacteria begin to spread systemically, thus initiating stage II.
126
what are the clinical features of Stage II (early disseminated Lyme disease)
1) Symptoms develop 3–10 weeks after a tick bite
2) Migratory arthralgia that can progress to Lyme arthritis
- -Spreads from one joint to another
- -Generally in large joints (especially knee or elbow)
3) Early neuroborreliosis
- -Cranial nerve disorders
- -Most commonly peripheral facial nerve palsy
- -Nocturnal radicular pain, paresthesia, and paresis
- -Meningitis
- -Polyneuropathy (mononeuritis multiplex, asymmetrical)
4) Lyme carditis
- -Risk of cardiac arrhythmias (e.g., AV Block) and rarely myopericarditis
5) Cutaneous manifestations
- -Multiple erythema migrans lesions
6) Ocular manifestations: including conjunctivitis, retinal vasculitis, optic neuropathy, and uveitis
127
what is the pathogenesis of neurological and cardiac manifestations?
combination of the presence of organism itself and immune response- lymphocytic infiltrates
128
what are the neurological manifestations of Lyme disease?
- Cranial nerve disorders
1) Most commonly peripheral facial nerve palsy
2) Nocturnal radicular pain, paresthesia, and paresis
- -Meningitis
- -Polyneuropathy (mononeuritis multiplex, asymmetrical)
129
what is the most characteristic manifestation fo stage 2 early Lyme disease?
Migratory arthralgia that can progress to Lyme arthritis
- -Spreads from one joint to another
- -Generally in large joints (especially knee or elbow)
130
how Lyme disease is diagnosed?
- -After a tick bite, observe for erythema chronicum migrans. Suspicious rashes may be monitored over several days.
- -If the patient history and clinical presentation indicate Stage I Lyme disease, empiric antibiotics may be started without further testing.
- -If symptoms of Lyme disease arise in a patient with possible exposure (especially if a history of recent travel to an area with high vector density) → conduct two-step serological testing
- -If signs of neuroborreliosis are present and other tests are inconclusive, consider additional procedures, such as a lumbar puncture for cerebrospinal fluid testing.
131
how Lyme disease is diagnosed serologically?
1) Initial test: enzyme‑linked immunosorbent assay (ELISA)
2) Confirmatory test: Western blot
3) Detect IgG and IgM antibodies against Borrelia
4) Results are only significant with corresponding clinical symptoms because:
- -Positive results only demonstrate exposure to Borrelia (not necessarily current infection).
- -False negative results are possible if seroconversion has not yet occurred (may take up to 8 weeks).
- -Various diseases can lead to a false positive serology as a result of cross-reactions, including:
* Syphilis
* Rocky Mountain spotted fever
* Systemic lupus erythematosus
* Rheumatoid arthritis
132
what diseases can yield false-positive serology for Lyme disease?
* Syphilis
* Rocky Mountain spotted fever
* Systemic lupus erythematosus
* Rheumatoid arthritis
133
what is the reason for the false-negative reaction for Lyme disease?
False-negative results are possible if seroconversion has not yet occurred (may take up to 8 weeks).
134
positive serological test necessariliy indicates current infection. True/False
Positive results only demonstrate exposure to Borrelia (not necessarily current infection).
135
what are other tests used in Lyme disease diagnosis?
1) Cerebrospinal fluid testing
- -Signs of lymphocytic meningitis, including elevated protein (due to a disrupted blood-brain barrier) and pleocytosis
- -Measure intrathecal IgG or IgM antibodies
2) Arthrocentesis
- -Commonly conducted if signs of arthritis are present, but results do not allow differentiation from septic arthritis without PCR
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what are the features of Stage III (late Lyme disease)
1) Symptoms develop months to years after the initial infection
2) Chronic Lyme arthritis (10% of cases)
- Lasts over a year and may be intermittent or persistent
- Typically in large joints (especially knee or elbow)
3) Late neuroborreliosis manifestations include:
- Aseptic (lymphocytic) meningitis
- Progressive encephalomyelitis
- Cognitive impairment
- Gait abnormality
- Bladder dysfunction
- Psychiatric abnormalities (e.g., depression, anxiety, bipolar disorder, etc.)
- Peripheral polyneuropathy
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what is the treatment of localized Lyme disease?
First-line oral antibiotics:
- Doxycycline
- Amoxicillin (first line in pregnants)
- Cefuroxime axetil
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what is the treatment of neuroborreliosis?
Intravenous antibiotics
- Drug of choice: ceftriaxone
- Cefotaxime
- Penicillin G
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what are the preventive measures against Lyme disease?
1) There is no approved vaccine on the market.
2) Avoid areas known for Lyme disease.
3) Prevent and properly manage tick bites to avoid exposure.
- -Wear protective clothing: e.g., long-sleeved shirts, long pants, and light colors.
- -Use tick repellent and pesticides.
- -Check the body for tick bites.
- -Remove ticks immediately!
* Grasp the tick with tweezers directly above the skin's surface.
* Carefully pull upward with even pressure.
* Do not use nail polish remover, adhesives, oils, or similar substances to remove the tick. The tick should be removed quickly rather than waiting for it to detach slowly.
* Disinfect the site of the bite and dispose of the tick
4) Observe the bite site for the early detection of EM.
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what tick repellent is used to avoid acquiring Lyme disease?
N,N-diethyl-meta-toluamide (DEET)
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Define Leptospirosis
The most common zoonotic disease worldwide. Caused by gram-negative Leptospira bacteria. Direct transmission to humans occurs when broken skin and mucous membranes come into contact with the urine of infected animals such as rodents. Usually self-limited but can progress to a severe form (icterohemorrhagic leptospirosis, or Weil's disease), which typically presents with a triad of jaundice, bleeding manifestations, and acute kidney injury.
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leptospira is a zoonosis. True/False
True
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what ar the reservoirs of leptospirosis?
wild & domestic mammals
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what ar ethe sources of leptospirosis?
Contaminated streams/ rivers/ lakes are usually the source of human infection
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Leptospirae can be transmitted from person to person. True/False
False
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how the rats spread the leptospira?
Causes chronic renal infection in the animal host: organisms shed in large numbers in urine
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what are the risk factors for acquiring leptospirosis?
- -Occupational groups at risk: farmers, sewer workers; water sports enthusiasts may also be affected.
- -Occupational exposure to infected animals
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how leptospira get entry to the human organism?
Penetrates skin through minor breaks in the epidermis OR crosses intact mucous membranes
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how leptospirae disseminates in the organism?
Organisms disseminate from the site of entry through the bloodstream and penetrate various tissues
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what are the pathological features in severe leptospirosis?
--In severe disease: vasculitis with blood vessel necrosis
Kidneys: diffuse tubulointerstitial inflammation and tubular necrosis
--Lungs: intra-alveolar hemorrhage
--Liver: damage to hepatocytes
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what are the immune-mediated responses seen in severe leptospirosis?
to immune-mediated responses such as meningoencephalitis or anterior uveitis
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what is the clinical manifestation of mild (anicteric) leptospirosis?
- -Clinical manifestations during the early phase are due to bacteremia
* High fever, headache
* Diarrhea, vomiting
* Conjunctivitis
* Rash
* Myalgias (especially in the calves and lower back)
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what is the incubation period of leptospirosis?
2-30 days
154
describe the features of biphasic leptospirosis
1) Initial spirochaetaemia- fever, headache, muscle pains, conjunctivitis
- -May resolve after 5- 7 days OR
2) May progress to immune phase with aseptic meningitis or Weil’s disease (severe form)
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what are the clinical manifestations of severe leptospirosis (Weil's disease)-10%
- -Clinical features are due to systemic spread and multiorgan involvement
- -Hepatitis → hepatomegaly, jaundice, acute liver failure
- -Hemorrhagic diathesis
- -Purpura due to thrombocytopenia
- -Pulmonary hemorrhage → hemoptysis
- -Acute kidney injury (interstitial nephritis, acute tubular necrosis) → oliguria, hematuria
- shock
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how much is the mortality of Weil's disease?
10-15%
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how leptospirosis is diagnosed?
- -Dark-field microscopy of urine or blood samples
- -Serological tests
- -PCR: detect leptospiral DNA in bodily fluids
- -Culture
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which test is the mainstay of the diagnosis of leptospirosis?
Serology (a mainstay of diagnosis in clinical practice)
| IgM positive in acute infection
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what is the role of PCR in the diagnosis of Leptospirosis?
- -PCR (only available in reference laboratories)
- -Blood early in illness (1st 7 days)
- -Urine stays positive for longer
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what is the treatment of leptospirosis?
1)for mild leptospirosis: aminopenicillins (ampicillin, amoxicillin), doxycycline
2)For severe leptospirosis
IV penicillin G (drug of choice), 3rd generation cephalosporins (e.g., ceftriaxone)
3)Supportive therapy for multiorgan failure
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what is the treatment of choice in severe leptospirosis?
IV penicillin G (drug of choice), 3rd generation cephalosporins (e.g., ceftriaxone)
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how leptospirosis is prevented?
- -Leptospirosis is a notifiable disease.
- -Disease control: implement appropriate pest control, vaccination of livestock and pets
- Avoid water sources, especially if skin abrasions or cuts
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is there vaccine against leptospirosis?
Vaccines exist for animals and humans but are not necessarily available in all areas. For example, vaccines may be offered to high-risk workers in some European and Asian countries (eg, rice workers in Italy) but are not available to US short-term travelers to endemic areas. No leptospirosis vaccine is available for human use in the United States, but there are vaccines for animals (pets and agricultural).
