Download leptospira

Introduction
Cell Biology
Transmission
Risk of transmission
Pathogenesis
Resistance
Disease
- Diagnosis
- sign and symptom
- clinical presentation
- Treatment
• Prevention
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Introduction
• leptospirosis has emerged as a health threat in new settings
due the influence of globalization and climate
• Endemic in tropical and subtropical regions .
• with an estimated 873,000 infections and 48,000 deaths
annually
Features of leptospira
Thin
Helically coiled
Motile spirochetes usually
6–20 μm in length .
The hooked ends of this
bacterium give its
distinctive question-mark
shape.
Dark field microscope; in
korthof’s media.
Transmission
Risk of Transmission
Localized in
jaundice
Uterus in
pregnant animal
abortion
Resistance
• Biofilms make liptospira more resistant to environmental
conditions , with the result that, more chances to survive and
infect humans .
Requirement of biofilms :
• 1- extensive reprogramming of transcription patterns along the
three replicons of L. biflexa and involves many regulatory
networks like c-di-GMP signaling, anti-anti-sigma factors.
• 2-canonical two-component systems that control basal
functions, like DNA metabolism and replication
• 3-more specific functions like cell motility or lipid and sugar
metabolisms
EtBr as an indicator to resistance
mechanisms .
• L. biflexa shows to possess a mechanical barrier, the outer
membrane (OM). hydrophilic agents, including EtBr and some
antibiotics, cannot diffuse into the periplasm.
• even though EtBr may enter via porins, leptospira can
prevent diffusion , by multidrug efflux pumps spanning both
the outer and the inner membranes
• inner-membrane single-drug transporters can contribute to the
efflux of EtBr back to the periplasm
Conclusion
• Overexpression of proteins involved in the process of drug
efflux or mutational gain of function in the genes encoding
these proteins contribute to antibiotic resistance in a number of
bacterial species .
Leptospirosis a kind of zoonotic
infectious
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Early diagnosis for the bacteria is very important because
the treatment is very effective in early stages.
Severity of the disease could be mild and self limiting to life
threatening condition.
• Nosogenic age: young and middle age,children.
S$S
Three symptoms:
fever, myalgia, fatigue;
 Three signs:
conjunctival suffusion
muscle tenderness
enlargement of lymph
nodes
Treatment
 Most cases of leptospirosis are self-limited in the
absence of antimicrobial therapy, although a
proportion of patients do develop severe
complications with significant morbidity and
mortality and need antimicrobial therapy .
 For inpatient : (SEVERE)
Penicillin G, ampicillin, amoxicillin, ceftriaxone or
cefotaxime and all are administered parentally.
 For outpatient : (MILD)
Doxycycline or azithromycin are enough
PREVENTION
Vaccines
The first demonstration has been provided in 1916 that immunisation with
killed leptospires protects against experimental infection.
Since then, whole Leptospira-based vaccines have been routinely
administered to livestock and domestic animals and used for
immunization of human populations . Whole Leptospira-based vaccines
are associated with high rates of advers reactions and confer only shortterm serovar-specific immunity .
Furthermore whole-Leptospira vaccines are not universally effective in
preventing carriage, which limits their use as a transmission blocking
intervention.
The availability of multiple genome sequences
provides an opportunity to apply high throughput
strategies for identifying novel vaccine candidates.
The ultimate goal for vaccine development will be to
identify a candidate which protects against the
spectrum of Leptospira agents.
Until epidemiologically-validated immune correlates
are identified, discovery of
vaccine candidates will likely continue to rely on the
search for new virulence factors and
outer membrane proteins.