Leptospirosis is a bacterial disease caused by Leptospira interrogans that is distributed worldwide but mostly affects populations in rural and semi-urban areas. It is transmitted through contact with water or soil contaminated by infected animal urine. Clinical presentation varies from mild flu-like symptoms to severe disease affecting multiple organs. Diagnosis involves serological tests, culture or PCR. Treatment is with doxycycline or penicillin with supportive care for organ complications. Prevention focuses on rodent control, vaccination of animals, and avoiding contact with contaminated water sources.
Leptospirosis is an infection caused by corkscrew-shaped bacteria called Leptospira. Signs and symptoms can range from none to mild such as headaches, muscle pains, and fevers; to severe with bleeding from the lungs or meningitis. If the infection causes the person to turn yellow, have kidney failure and bleeding, it is then known as Weil's disease.If it causes lots of bleeding into the lungs then it is known as severe pulmonary hemorrhage syndrome.
Up to 13 different genetic types of Leptospira may cause disease in humans. It is transmitted by both wild and domestic animals. The most common animals that spread the disease are rodents.[7] It is often transmitted by animal urine or by water or soil containing animal urine coming into contact with breaks in the skin, eyes, mouth, or nose. In the developing world the disease most commonly occurs in farmers and poor people who live in cities. In the developed world it most commonly occurs in those involved in outdoor activities in warm and wet areas of the world.Diagnosis is typically by looking for antibodies against the bacterium or finding its DNA in the blood
Leptospirosis is an infection caused by corkscrew-shaped bacteria called Leptospira. Signs and symptoms can range from none to mild such as headaches, muscle pains, and fevers; to severe with bleeding from the lungs or meningitis. If the infection causes the person to turn yellow, have kidney failure and bleeding, it is then known as Weil's disease.If it causes lots of bleeding into the lungs then it is known as severe pulmonary hemorrhage syndrome.
Up to 13 different genetic types of Leptospira may cause disease in humans. It is transmitted by both wild and domestic animals. The most common animals that spread the disease are rodents.[7] It is often transmitted by animal urine or by water or soil containing animal urine coming into contact with breaks in the skin, eyes, mouth, or nose. In the developing world the disease most commonly occurs in farmers and poor people who live in cities. In the developed world it most commonly occurs in those involved in outdoor activities in warm and wet areas of the world.Diagnosis is typically by looking for antibodies against the bacterium or finding its DNA in the blood
Leptospirosis is a worldwide public health problem. In humid tropical and subtropical areas, where most developing
countries are found, it is a greater problem than in those with a temperate climate. The magnitude of the problem in
tropical and subtropical regions can be largely attributed to climatic and environmental conditions but also to the
great likelihood of contact with a Leptospira-contaminated environment caused by, for example, local agricultural
practices and poor housing and waste disposal, all of which give rise to many sources of infection. In countries with
temperate climates, in addition to locally acquired leptospirosis, the disease may also be acquired by travellers
abroad, and particularly by those visiting the tropics.
Leptospirosis is a potentially serious but treatable disease. Its symptoms may mimic those of a number of other
unrelated infections such as influenza, meningitis, hepatitis, dengue or viral haemorrhagic fevers. Some of these
infections, in particular dengue, may give rise to large epidemics, and cases of leptospirosis that occur during such
epidemics may be overlooked. For this reason, it is important to distinguish leptospirosis from dengue and viral
haemorrhagic fevers, etc. in patients acquiring infections in countries where these diseases are endemic. At present,
this is still difficult, but new developments may reduce the technical problems in the near future. It is necessary,
therefore, to increase awareness and knowledge of leptospirosis as a public health threat.
Leptospirosis is a bacterial disease that affects humans and animals. It is caused by bacteria of the genus Leptospira. In humans, it can cause a wide range of symptoms, some of which may be mistaken for other diseases. Some infected persons, however, may have no symptoms at all.
Brucellosis, a bacterial disease caused by members of the genus Brucella, is an important zoonosis and a significant cause of reproductive losses in animals.
Leptospirosis is a worldwide public health problem. In humid tropical and subtropical areas, where most developing
countries are found, it is a greater problem than in those with a temperate climate. The magnitude of the problem in
tropical and subtropical regions can be largely attributed to climatic and environmental conditions but also to the
great likelihood of contact with a Leptospira-contaminated environment caused by, for example, local agricultural
practices and poor housing and waste disposal, all of which give rise to many sources of infection. In countries with
temperate climates, in addition to locally acquired leptospirosis, the disease may also be acquired by travellers
abroad, and particularly by those visiting the tropics.
Leptospirosis is a potentially serious but treatable disease. Its symptoms may mimic those of a number of other
unrelated infections such as influenza, meningitis, hepatitis, dengue or viral haemorrhagic fevers. Some of these
infections, in particular dengue, may give rise to large epidemics, and cases of leptospirosis that occur during such
epidemics may be overlooked. For this reason, it is important to distinguish leptospirosis from dengue and viral
haemorrhagic fevers, etc. in patients acquiring infections in countries where these diseases are endemic. At present,
this is still difficult, but new developments may reduce the technical problems in the near future. It is necessary,
therefore, to increase awareness and knowledge of leptospirosis as a public health threat.
Leptospirosis is a bacterial disease that affects humans and animals. It is caused by bacteria of the genus Leptospira. In humans, it can cause a wide range of symptoms, some of which may be mistaken for other diseases. Some infected persons, however, may have no symptoms at all.
Brucellosis, a bacterial disease caused by members of the genus Brucella, is an important zoonosis and a significant cause of reproductive losses in animals.
Pars Planitis is a disease of the eye that is characterized by inflammation of the narrowed area (pars plana) between the colored part of the eye (iris) and the choroid. This may lead to blurred vision; dark, floating spots in the vision; and progressive vision loss.
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
2. Epidemiology
• Distributed worldwide but mostly in the tropic
• mostly affect populations in rural settings and semi-urban
slums
• Global annual incidence of endemic human leptospirosis: 5
cases per 100 000 population
• Limited studies have suggested that the median annual
incidence:
per 100 000 population
– African Region 95.5
– Western Pacific 66.4
– Americas 12.5
– South-East Asia 4.8
– Europe 0.5
• 5 to 30% of mortality
3. Number of Leptospirosis cases
2004 - 2010
YEAR CASE DEATH
2004 263 20
2005 378 20
2006 527 22
2007 949 22
2008 1263 47
2009 1418 62
2010 1976 69
Source: Report of Morbidity & Mortality for Inpatient for the year
2004-2010 ( PER-PD206); Health Informatics Centre, MOH
4.
5.
6. Outbreak
• Examples of outbreak:
- athletes competing in the Eco-Challenge-Sabah 2000 in
Malaysia; 44% of those who reported feeling ill met the
case definition of leptospirosis. Significant risk factors
included kayaking and swimming in and swallowing
water from the Segama River
-Recreational area in Maran, Pahang in June 2010
- 83 people involved in a search mission after one
person went missing (drowned)
-22 suspected with leptospirosis. 8 persons
died
7. Outbreak in Sarawak 2011
• 148 cases of leptospirosis were recorded from Jan 1 to
Dec 15 (2011), a significant increase considering that
only 49 cases were recorded for the whole of 2010.
-1st outbreak happened at SMK Bandar Baru
Bintangor. 114 students were inflicted with mild flu-
like illness.
- 2nd outbreak involved 5 army recruits after they had
attended a training exercise in Lundu
Read more: http://www.theborneopost.com/2011/12/27/13-die-of-leptospirosis-in-sarawak-this-year/#ixzz1rylzqZih
8. • Epidemics are typically seen during flooding, and
changing environmental trends
• Underreported – misdiagnosed/ undiagnosed
• Age-more in 20-30 years old, rare in young
children and infant- due to low exposure.
• Children are particularly vulnerable to serious
forms of the disease.
• Sex- male > female-greater occupational
exposure to infected animals and contaminated
environment
9. Introduction
• A notifiable disease in Malaysia
• Caused by pathogenic spirochete of the genus leptospira
• L.interrogans
• L.biflexa.
• Others
• Leptospira strains have been divided into 23 sub groups
• Pathogenic or saprophytic leptospires.
• Each sub-group consists of several strains designated as
serovars.
• More than 260 serovars identified. 37 serovars in M’sia.
10. Leptospira interrogans
• A species of genus Leptospira
• Gram negative obligate aerobe spirochete
• Finely coiled, thin, motile
• Periplasmic flagellum for mobility
• 2 important pathogenic serovars from this species
are Canicola and Icterohaemorrhagiae.
• reside in alkaline water, alkaline soil- survive in
these area for months or years
• also could be found in urine
11. Mode of transmission
• Leptospira bacteria have been found in dogs, rats, livestock,
mice, rabbits, frogs, fish, snakes, and certain birds and insects.
• Transmission- direct contact with urine
- contact with soil, water, or plants that have been
contaminated by animal urine.
• Leptospira bacteria can enter the body through cuts or skin
damage areas or through mucous membranes.
12.
13.
14.
15. Pathophysiology
• Gains entry via intact skin or mucosa.
• Multiplies in blood and tissue.
• Spread to any part of the body but particularly affects the
liver and kidney.
• Kidney- migrates to the interstitium, renal tubules, and
tubular lumen, causing interstitial nephritis and tubular
necrosis.
• Renal failure- Usually due to tubular damage
– hypovolemia from dehydration & altered capillary
permeability
• Liver –Centrilobular necrosis with proliferation of Kupffer
cells. Jaundice due to hepatocellular dysfunction.
• Skeletal muscle- causing edema, vacuolization of myofibrils,
and focal necrosis.
16. • Muscular microcirculation is impaired and capillary
permeability is increased, with resultant fluid leakage
and circulatory hypovolemia
• Disseminated vasculitic syndrome may result from
damage to the capillary endothelium.
• Invade aqueous humor of the eye, may persist for
many months, occ lead to chronic or recurrent
uveitis.
• The disease is most often self-limited and nonfatal.
• Systemic immune response may eliminate the organism
from the body but may also lead to a symptomatic
inflammatory reaction that can produce secondary end-
organ injury
17. Clinical Features
• incubation period -2 - 30 days (average 10 days)
• 2phases: (< 50% of cases)
• Begins with flu-like symptoms then briefly asymptomatic
until the second phase begins.
• First phase(1 week ): Septicaemic/ Leptospiremia phase
• Organism may be isolated from blood cultures,
cerebrospinal fluid (CSF), and most tissues.
• High, remittent fever(38-40oC)
• Retroorbital headache, chills and rigors
• Myalgia : paraspinal, calf, abdominal muscle
• Conjuctival suffusion
• Maculopapular/ purpuric skin rashes
• Vomitting
18. • Second stage - immune or leptospiruric stage
– Body's immunologic response to infection
– Circulating antibodies may be detected
– Organism may be isolated from urine
– It may not be recoverable from blood or CSF.
– Lasts 4-30 days
– Disease referable to specific organs is seen.
– These organs include the meninges, liver, eyes, and kidney.
• Nonspecific symptoms, i.e fever and myalgia, less severe than
in the first stage and last a few days to a few weeks.
• Aseptic meningitis is the most important clinical syndrome
observed in the immune anicteric stage.
-lasts a few days but occasionally lasts 1-2 weeks.
• Meningeal symptoms develop in 50% of patients.
• Mild delirium may also be seen.
• Weil’s disease
20. Anicteric leptospirosis
•milder form of the disease.
•Almost 90% of patients have this type of illness.
• Patients have fever, myalgia but do not have jaundice.
remittent fever with chills
- Calf, abdominal & lumbosacral muscles are very
painful & severely tender.
• May have conjunctival suffusion- usually bilateral, most
marked on palpebral conjunctiva, it may be associated
with unilateral or bilateral conjunctival haemorrhage.
21. Other manifestations
•Usually intense headache, sometimes throbbing, commonly
in frontal region, often not relieved by analgesics.
•Renal- usually asymptomatic urinary abnormality i.e mild
proteinuria with few casts & cells in the urine.
•Pulmonary- cough & chest pain and in few cases by
haemoptysis.
•Hemorrhagic tendencies are also present in some patients
•All the clinical features either decrease or disappear within 2
to 3 days and then they reappear.
•DDX: malaria, dengue hemorrhagic fever, viral hepatitis etc.
•In endemic area all cases of fever with myalgia and
conjunctival suffusion should be considered as suspected
cases of leptospirosis.
22. Icteric leptospirosis
•It is the severe form of the disease.
• It is characterized by jaundice and is usually
associated with involvement of other organs.
• About 5-10% of patients have these type of
manifestations.
• profound jaundice
• renal dysfunction
• hepatic necrosis
• pulmonary dysfunction
• hemorrhagic diathesis
23. SSX
• General - rash, fever, bleeding, signs of
hypovolemia/cardiogenic shock
• Icteric - Jaundice, hepatomegaly, abdominal tenderness
• Pulmonary - Cough, hemoptysis, dyspnea, respiratory distress
• Neurologic - Cranial nerve palsies, confusion, changes in
consciousness, delirium, other signs of meningitis
• Ocular - Subconjunctival hemorrhage, uveitis, signs of
iridocyclitis or chorioretinitis
• Hematologic - Bleeding, petechiae, purpura, ecchymosis,
splenomegaly
• Cardiac - Signs of congestive heart failure, pericarditis
24.
25. Investigations
• WBC increased - 3-26/microL; Thrombocytopenia
uncommon.
• CK elevated markly
• UFEME: proteinuria, pyuria, granular casts and occasionally
microscopic hematuria
• LFT: deranged ALT,AST in 40%, usually < 200IU/L, jaundice
in weil’s syndrome
• BUSE: Hyponatremia, hypokalemia
• CSF - neutrophilic or lymphocytic pleocytosis with minimal
to moderately elevated protein and normal glucose.
• CXR- show small nodular densities, which can progress to
confluent consolidation or a ground glass appearance
– alveolar hemorrhage, ARDS, or pulmonary edema
26. Diagnosis
• Culture from clinical specimen
– Blood- within 10 days
– CSF Within 5 - 10 days
– Urine within 10-30 days
• Serology-Rapid test, MAT(gold standard ), ELISA
– 4X rise in titres between acute and convalescent-phase
– A single titer of >1:800 is strong evidence of current or
recent infection with leptospira
– rapid tests, the microplate IgM ELISA and an IgM dot-ELISA
dipstick test
• polymerase chain reaction (PCR)
29. CASE CLASSIFICATION
Leptospirosis is difficult to distinguish from a number of other diseases on clinical
grounds alone. History of possible exposure is paramount to aid clinical diagnosis.
Clinical case
A case that is compatible with the following clinical description:
Acute febrile illness with history of exposure to water and/or environment
possibly contaminated with infected animal urine with ANY of the following
symptoms:
• Headache
• Myalgia particularly associated with the calf muscles and lumbar region
• Arthralgia
• Conjunctival suffusion
• Meningeal irritation
• Anuria or oliguria and/or proteinuria
• Jaundice
• Hemorrhages (from the intestines and lungs)
• Cardiac arrhythmia or failure
• Skin rash
• GI symptoms such as nausea, vomiting, abdominal pain, diarrhea
30. CASE CLASSIFICATION
Probable Case
A clinical case AND positive ELISA/other Rapid tests.
Confirmed case:
A confirmed case of leptospirosis is a suspected OR probable case with any
one of the following laboratory tests:
• Microscopic Agglutination Test (MAT),
– For single serum specimen - titre 1:400
– For paired sera - four fold or greater rise in titre
• Positive PCR
• Positive culture for pathogenic leptospires
• Demonstration of leptospires in tissues using immunohistochemical staining
• In places where the laboratory capacity is not well established, a case can be
considered as confirmed if the result is positive by two (2) different rapid
diagnostic tests.
31. Treatment
• Majority of the infection are self limiting
• Antibiotic
– Shorter duration of illness/ hospital stay, prevent
urinary shedding, rapid resolution of organ
impairment
• General supportive care
• Treatment of complication
32. Antibiotic
• Mild/ outpatient
Doxycycline 100mg BD X 1/52 (2mg/kg/day) Or
Ampicillin 500-750mg 6hourly X 1/52 Or
Amoxicillin 500mg 6hrly X 1/52
• Severe Disease:
IV penicillin G 1.5MU 6hourly X 1/52 Or
IV Ceftriaxone 1g OD X 1/52 Or
IV Cefotaxime 1g 6 hourly
34. penicillin allergy:-
• azithromycin (10 mg/kg on D1; max dose 500 mg/day,
followed by 5 mg/kg/day OD ; max dose 250 mg/day)
Or
• clarithromycin (15 mg/kg/day divided in two equal doses;
max dose 1 g/day).
Jarisch-Herxheimer reaction
• Rare complication of treatment
• release of endotoxin-like substances when large numbers
of spirocete are killed by antibiotics
• It is manifested by fever, chills, rigor, hypotension,
headache, tachycardia, hyperventilation, vasodilation with
flushing, myalgia.
• It should be treated supportively
35. Supportive care
• Patients with renal failure may require dialysis;
renal function is restored in most.
• Those with Weil syndrome may need
transfusions of whole blood, platelets, or
both.
• Supportive therapy and careful management
of renal, hepatic, hematologic, and CNS
complications are important.
36. Notification
• All probable and confirmed cases must be
notified to the nearest Health District Office
within 1 week of the date of diagnosis.
• Notification of cases can be done using Rev/ 2010
form
• All notified cases must be investigated using the
Investigation Form
37.
38. Prevention
• Vaccination of domestic animals against leptospirosis provides
substantial protection, but is not effective in 100 percent of
animals.
• Vaccine for human not widely avaiable. Vaccines commercially
available – icterohaemorrhagiae, hardjo, pomona.
• The major control measure available for humans
– to avoid potential sources of infection such as stagnant water, water
derived from run off from animal farms
– rodent control
– protection of food from animal contamination.
39. Prophylaxis
Pre-exposure Prophylaxis
• May be considered for people at high risk of exposure to potentially
contaminated sources e.g. soldiers going into jungles, rescue team
• Dose:
Doxycycline 200mg stat dose then weekly throughout the stay
OR
Azithromycin 500mg stat dose then weekly throughout the stay (For
pregnant women and those who are allergic to Doxycycline)
• However the benefit of pre-exposure prophylaxis remains
controversial where possible benefits need to be balanced with
potential side effects (e.g. doxycycline induced photosensitivity,
nausea, etc.)
40. Prophylaxis
Post-Exposure
• In an outbreak, there may be a role for post exposure
prophylaxis for those exposed to a common source as
the index case.
Dose:
• Doxycycline 200mg stat dose then followed by 100mg
BD for 5 – 7 days for those symptomatic with the first
onset of fever.
OR
• Azithromycin 1gm on Day-1, followed by Azithromycin
500mg daily for 2 days
(For pregnant women and those who are allergic to
Doxycycline)
41.
42. Reference
• Guideline for the diagnosis, management, prevention
and Control of leptospirosis in Malaysia. Disease
Control Division, Department of Public Health, MOH
Malaysia. 2011 1st edition
• www.uptodate.com
• Guidelines for prevention and control of Leptospirosis,
zoonosis division, National institute of communicable
disease, Delhi 2006
• Soo, Lau, Chew, Hu. Sarawak Handbook of Medical
Emergencies, 3rd edition, CE publication, 2011.
• http://www.who.int/topics/leptospirosis/en