PBL 2

1.

Discuss the epidemiology of Leptospirosis in the Caribbean.

http://www.merckmanuals.com/professional/infectious_diseases/spirochetes/leptospirosis.html?qt=Le
ptospirosis&alt=sh
http://www.merckmanuals.com/home/infections/bacterial_infections/leptospirosis.html?qt=Leptospiro
sis&alt=sh
http://www.hopkinsguides.com/hopkins/ub/citation/3629704/The_incidence_of_severe_leptospirosis_i
n_Trinidad_
http://www.tropicalmedandhygienejrnl.net/article/0035-9203(76)90008-0/abstract

1987 The incidence of severe leptospirosis in Trinidad

(annual average 26 or 2.6 per 100,000 population

Leptospirosis in Trinidad and Grenada, with special

reference to the mongoose 1972
Transactions of the Royal Society of Tropical Medicine and Hygiene
Five Canicola strains of Leptospira were isolated from mongooses in Trinidad, and serological studies showed that
this was the most common serogroup from mongooses on the island.

Leptospirosis has a worldwide distribution and is more spread in tropical regions than in temperate
countries
Annual rates of infection vary from 0.02 per 100,000 in temperate climates to 10 to 100 per 100,000 in
[15]
tropical climates.
[16]

Nepal is experiencing a leptospirosis outbreak as of August 2010, having favorable conditions like
warm temperatures and moist soils. Cases increase in summer months (monsoon), but no accurate case
[17]
count has been made as most go unreported. Almost all the higher animals and rodent hosts of
Leptospira occur in Nepal.
Leptospirosis is now being recognized as a re-emerging infectious disease.

An association between prevalence of leptospirosis and gender has been reported in many studies.
Particularly, men tend to present much higher incidence or prevalence of the disease than women and
this fact was not attributed to more frequent exposure of men

Leptospirosis is a zoonotic disease caused by bacteria of the genus Leptospira. It is most commonly spread via
water contaminated with urine from infected animals, but contaminated food or soil can also act as vehicles for the
disease. The main animal reservoirs are rodents, livestock and dogs. Disease in humans can vary from mild flu-like
illness to serious disease. Some severe complications include kidney damage, liver failure, respiratory distress,
meningitis and death.
Although Leptospirosis can occur worldwide, there are a number of risk factors associated with the disease. It is
most common in urban slum areas, where there is inadequate sewage disposal and water treatment. It can also
be an occupational hazard for those working outdoors or with animals and a recreational hazard for those
participating in water-related activities. Epidemics are typically seen during flooding, and changing environmental
trends, with extreme weather patterns, may perpetuate these epidemics.

What do we still need to know?

Very little is currently known regarding the true incidence of Leptospirosis. It is estimated that 0.1 to 1 per 100 000
people living in temperate climates are affected each year, with the number increasing to 10 or more per 100 000
people living in tropical climates. If there is an epidemic, the incidence can soar to 100 or more per 100 000 people.
The disease is underreported for many reasons, including difficulty in distinguishing clinical signs from those of
other endemic diseases and a lack of appropriate diagnostic laboratory services.

LEPTOSPIROSIS IN TRINIDAD AND TOBAGO: EPIDEMOILOGY AND DEVELOPMENT OF AN EFFECTIVE VACCINE FOR
USE IN DOGS
UWI St Augustine Project
Leptospirosis is a zoonotic disease with a worldwide distribution caused by pathogenic serovars (subspecies) of the
genus Leptospira. In recent years in Trinidad and Tobago, as well as in other countries in the Caribbean region,
there has been an increase in the incidence of human leptospirosis and fatalities causing anxiety in the various
populations. There are also reports from field veterinarians in Trinidad and Tobago of observed increase in clinical
leptospirosis in properly vaccinated dogs suggesting that the vaccines used in the country may have doubtful
efficacy. These reports indicate that these vaccines may not contain the serovars of Leptospira responsible for
canine leptospirosis in the country. The investigation in human and animal (dogs, livestock and wildlife)
populations in the country is designed to identify important risk factors for exposure, to determine the prevalence
and epidemiology of leptospirosis, to identify the predominant serovar(s) involved in subclinical and clinical
leptospirosis, to establish temporal and spatial distribution of cases and serovars using geographical information
system (GIS), to characterize the Leptospira isolates using molecular methods, to determine their virulence,
pathogenicity and resistance to antimicrobial agents, and finally to develop an effective vaccine for use in dogs in
the country.

2.

Discuss the mode of transmission and treatment of Leptospirosis.

http://en.wikipedia.org/wiki/Leptospirosis#Epidemiology

Transmitted

Though the organism can affect any organ of the body, the kidney and liver are commonly involved. The incubation
period is usually 10 days. It may vary from 2-20 days.

symptoms in humans appear after a 414 day incubation period. (Wiki)

The incubation period ranges from 2 to 20 (usually 7 to 13) days (Merk)

Outbreaks of leptospirosis are usually caused by exposure to water contaminated

with the urine of infected animals. Many different kinds of animals carry the
bacterium; they may become sick but sometimes have no symptoms. Leptospira
organisms have been found in cattle, pigs, horses, dogs, rodents, and wild animals.
Humans become infected through contact with water, food, or soil containing urine
from these infected animals. This may happen by swallowing contaminated food or
water or through skin contact, especially with mucosal surfaces, such as the eyes or
nose, or with broken skin. The disease is not known to be spread from person to
person. BUT They can be transmitted from human to human by sexual intercourse, transplacentally
from the mother to the fetus and via breast milk to a child. Urine from a patient suffering from leptospirosis
should be considered infectious. As leptospires can be cultured from blood, this should be viewed as
infectious for some time before the onset of symptoms and during the first 710 days of illness (WHO)
Leptospirosis is transmitted by the urine of an infected animal and is contagious as long as it is still
moist. Although rats, mice and moles are important primary hosts, a wide range of other mammals
including dogs, deer, rabbits, hedgehogs, cows, sheep, raccoons, possums, skunks, and certain
marine mammals are able to carry and transmit the disease as secondary hosts. Dogs may lick the urine
of an infected animal off the grass or soil, or drink from an infected puddle. There have been reports of
"house dogs" contracting leptospirosis apparently from licking the urine of infected mice that entered the
house. The type of habitats most likely to carry infective bacteria are muddy riverbanks, ditches,
gullies, and muddy livestock rearing areas where there is regular passage of either wild or farm
mammals. There is a direct correlation between the amount of rainfall and the incidence of leptospirosis,
making it seasonal in temperate climates and year-round in tropical climates.
[8]

Leptospirosis is also transmitted by the semen of infected animals. Slaughterhouse workers

may contract the disease through contact with infected blood or body fluids.
Leptospirosis is common among water-sport enthusiasts in specific areas as prolonged
immersion in water is known to promote the entry of the bacteria. Surfers and whitewater
[9]
paddlers are at especially high risk in areas that have been shown to contain the bacteria, and can
contract the disease by swallowing contaminated water, splashing contaminated water into their eyes or
[10]
nose, or exposing open wounds to infected water. Occupations at risk include veterinarians,
slaughterhouse workers, farmers, sewer workers, and people working on derelict buildings. Rowers are
also sometimes known to contract the disease.

Leptospirosis usually occurs in two phases:

First phase: About 2 to 20 days after infection occurs, fever, headache, nausea, vomiting, severe muscle aches
in the calves and back, and chills occur suddenly. The eyes usually become very red on the third or fourth day.
Some people cough, occasionally bringing up blood, and have chest pain. Most people recover within 1 week.

Second (immune) phase: In some people, symptoms recur a few days later. They result from inflammation
caused by the immune system as it eliminates the bacteria from the body. The fever returns, and the space within
the tissues covering the brain and spinal cord (meninges) often becomes inflamed. This inflammation (meningitis)
causes a stiff neck and headache.

Treatment
Penicillin

Doxycycline

The antibiotic doxycycline can prevent leptospirosis. It is given to people who were exposed to the
bacteria at the same time as people who have been infected
Mild infections are treated with antibiotics such as amoxicillin or doxycycline, given by mouth. For severe
infections, antibiotics such as penicillin, doxycycline, or erythromycin may be given intravenously. Fluids
containing salts may also be given. People with the infection do not have to be isolated, but care must be
taken when handling and disposing of their urine.
People with Weil's syndrome ((icteric Jaundie leptospirosis) is a severe form with jaundice and usually
azotemia, anemia, diminished consciousness, and continued fever) may need blood transfusions and
hemodialysis.
Antibiotic therapy is most effective when begun early in the infection. In severe illness, penicillin G 5 to 6
million units IV q 6 h or ampicillin 500 to 1000 mg IV q 6 h is recommended. In less severe
cases, doxycycline 100 mg po q 12 h, ampicillin 500 to 750 mg po q 6 h, or amoxicillin 500 mg po q 6 h
may be given for 5 to 7 days. In severe cases, supportive care, including fluid and electrolyte therapy, is
also important. Doxycycline 200 mg po given once/wk during a period of known geographic exposure
prevents disease.
There are no human vaccines; animal vaccines are only for a few strains, and are only effective for a few
months

3. Discuss the results of a LFT in leptospirosis.

http://www.jpgmonline.com/article.asp?issn=00223859;year=2005;volume=51;issue=3;spage=195;epage=200;aulast=Ahmad

LFT - a moderate elevation of transaminases. Brief elevations of aspartate aminotransferase (AST),

alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) levels are relatively mild. These
levels may be normal, even in children with jaundice
Liver function tests (LFT) show a slight elevation in aminotransferases (AST and ALT), bilirubin, and
alkaline phosphatase
In icteric (jaundice) leptospirosis, liver function tests (LFT) generally show a significant rise in
bilirubin, with lesser increase in transaminases (ALT and ALT) and marginal increase in alkaline
phosphatase levels. The hyperbilirubinemia is generally out of proportion to the other liver function
test values. Serum amylase may also be elevated, particularly in patients with acute renal failure.

Serum bilirubin is elevated out of proportion to elevations in serum aminotransferases. In jaundiced

patients, bilirubin levels are usually < 20 mg/dL (< 342 mol/L) but may reach 40 mg/dL (684 mol/L) in
severe infection.
Aside: The erythrocyte sedimentation rate (ESR) is elevated in anicteric disease, and white cell
counts (WBC) range from below normal to moderately elevated. Urinalysis shows proteinuria, pyuria
(pus in the urine), and often microscopic hematuria. Hyaline and granular casts may also be present
during the first week of illness.

4. List the complications of Leptospirosis.

Complications include meningitis, extreme fatigue, hearing loss, respiratory distress, azotemia
(uremia:urea in the blood), and renal interstitial tubular necrosis, which results in renal failure and
often liver failure (the severe form of this disease is known as Weil's disease, though it is sometimes
[13]
named Weil Syndrome). Cardiovascular problems are also possible.
Pulmonary complications and death occur in a low percentage of patients with leptospirosis. Delayed antibiotic
treatment and thrombocytopenia are risk factors for the development of pulmonary involvement in leptospirosis.
Leptospirosis during pregnancy may lead to fetal death, spontaneous abortion, stillbirth, and congenital
leptospirosis
Aseptic meningitis is a common manifestation during the immune phase; it usually presents with severe headaches,
with or without delirium. Analysis of cerebrospinal fluid discloses lymphocytic pleocytosis with cell counts below 500
cells/mm^3. CSF glucose is normal and protein is mildly elevated.
Neuropsychiatric manifestations include headache, paresis (partial/incomplete paralysis), paralysis, mood swings,
and depression
Ophthalmic complications (eye) of leptospirosis include uveitis (inflammation of the uveal tract: iris, ciliary body,
choroid) and iridocyclitis (inflammation of iris and ciliary body)

pancreatitis

pulmonary haemorrhage

In the kidneys, interstitial nephritis, tubular necrosis, and impaired capillary permeability, as well as the
associated hypovolemia, result in renal failure.
Liver involvement is marked by centrilobular necrosis and Kupffer cell proliferation, with hepatocellular
dysfunction.
Pulmonary involvement is secondary to alveolar and interstitial vascular damage resulting in
hemorrhage. This complication is considered to be the major cause of leptospirosis-associated death.

The skin is affected by epithelial vascular insult.

Skeletal muscle involvement is secondary to edema, myofibril vacuolization, and vessel damage.
The damage to the vascular system as a whole can result in capillary leakage, hypovolemia, and shock.
Many patients with leptospirosis may develop disseminated intravascular coagulation (DIC), hemolytic
uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and vasculitis.
Thrombocytopenia indicates severe disease and should raise suspicion for a risk of bleeding.[2, 3]
Clinical manifestations of leptospirosis after the acute infection are the result of the inflammatory
response, as well as action of the remaining organisms in the aqueous humor.

5. Discuss the natural history and pathogenesis of Lepto.

http://emedicine.medscape.com/article/220563-overview#a0104

Leptospirosis is a disease that is caused by pathogenic spirochetes of the genus Leptospira. It is

considered the most common zoonosis in the world. Leptospirosis has recently been recognized as a reemerging infectious disease among animals and humans[1] and has the potential to become even more
prevalent with anticipated global warming. Leptospirosis is distributed worldwide (sparing the polar
regions) but is most common in the tropics.
Humans and a wide range of animals, including mammals, birds, amphibians, and reptiles can
develop Leptospira infection. However, humans are rarely chronic carriers and are therefore considered
accidental hosts. Leptospirosis is transmitted via direct contact with the body fluid of an acutely infected
animal or by exposure to soil or fresh water contaminated with the urine of an animal that is a chronic
carrier.
Human leptospirosis is often acquired via contact with fresh water contaminated by bovine, rat, or canine
urine as part of occupational contact with these animals. The disease is also acquired during adventure
travel or vacations that involve water sports or hiking, or even as a consequence of flooding.
The burgeoning exotic-pet trade further increases the likelihood of transmission. In 2005, leptospirosis
was transmitted from southern flying squirrels imported from Miami, Florida, to two Japanese animal
handlers employed by an importer of exotic pets. Endemic canine leptospirosis is becoming more
common in the United States, and California has seen a re-emergence of disease since 2000.
Leptospirosis in humans is characterized by an acute febrile illness followed by mild self-limiting sequelae
or an even more severe, and often fatal, multiorgan involvement.

The disease was first described by Larrey in 1812 offivre jaune among Napoleon's troops at the
siege of Cairo. It was initially believed to be related to the plague but not as contagious.
Throughout the remainder of the 19th century, the illness was known in Europe as bilious typhoid.
A little over 100 years ago, Adolph Weil published his historic paper describing the most severe
form of infection that would be later known as Weil disease.
In 1907, special staining techniques were used to confirm that a spirochete was responsible for
this illness. A postmortem examination of the kidney of a person with Weil disease contained a
spiral organism with hooked ends, which was first named Spirochaeta interrogans.

PATHOPHYSIOLOGY
The leptospires are thin, coiled, gram-negative, aerobic organisms 6-20 m in length. They are motile,
with hooked ends and paired axial flagella (one on each end), enabling them to burrow into tissue. Motion
is marked by continual spinning on the long axis. They are unique among the spirochetes in that they can
be isolated on artificial media.
Leptospires belong to the order Spirochaetales and the family Leptospiraceae. Traditionally, the
organisms are classified based on antigenic differences in the lipopolysaccharide envelopes that
surround the cell wall. Serologic detection of these differences, therefore, is based on identifying serovars
within each species. Based on this system, the genus Leptospira contains two speciesthe
pathogenic Leptospira interrogans, with at least 218 serovars, and the nonpathogenic, free-living,
saprophytic Leptospira biflexa, which has at least 60 serovars.
Current studies that classify the organisms based on DNA relatedness identify at least 7 pathogenic
species of leptospires. However, organisms that are identical serologically may be different genetically,
and organisms with the same genetic makeup may differ serologically. Therefore, some authors feel that
the traditional serologic system is the most useful from a diagnostic and epidemiologic standpoint.
Although not fully understood, leptospires are believed to enter the host through abrasions in healthy skin,
through sodden and waterlogged skin, directly through intact mucus membranes or conjunctiva, through
the nasal mucosa and cribriform plate, through the lungs (after inhalation of aerosolized body fluid), or
through the placenta during pregnancy. Virulent organisms in a susceptible host gain rapid access to the
bloodstream through the lymphatics, resulting in leptospiremia and spread to all organs. The incubation
period is usually 5-14 days but has been described from 72 hours to a month or more.
If the host survives the acute infection, septicemia and multiplication of the organism persist until the
development of opsonizing immunoglobulin in the plasma, followed by rapid immune clearance. However,
after clearance from the blood, leptospires remain in immunologically privileged sites, including the renal
tubules, brain, and anterior chamber of the eye, for weeks to months. In humans, leptospires in the renal
tubules and resulting leptospiruria rarely persist longer than 60 days.
During acute infection, leptospires are thought to multiply in the small blood vessel endothelium, resulting
in damage and vasculitis. The major clinical manifestations of the disease are believed to be secondary to
this mechanism, which can affect nearly any organ system.

In the kidneys, interstitial nephritis, tubular necrosis, and impaired capillary permeability, as well as the
associated hypovolemia, result in renal failure.
Liver involvement is marked by centrilobular necrosis and Kupffer cell proliferation, with hepatocellular
dysfunction.
Pulmonary involvement is secondary to alveolar and interstitial vascular damage resulting in
hemorrhage. This complication is considered to be the major cause of leptospirosis-associated death.
The skin is affected by epithelial vascular insult.
Skeletal muscle involvement is secondary to edema, myofibril vacuolization, and vessel damage.
The damage to the vascular system as a whole can result in capillary leakage, hypovolemia, and shock.
Many patients with leptospirosis may develop disseminated intravascular coagulation (DIC), hemolytic
uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and vasculitis.
Thrombocytopenia indicates severe disease and should raise suspicion for a risk of bleeding.[2, 3]
Clinical manifestations of leptospirosis after the acute infection are the result of the inflammatory
response, as well as action of the remaining organisms in the aqueous humor.

6.

Discuss kidney function tests in Lepto.

Elevated serum creatinine

7. Discuss the pharmacology of dobutamine.

http://en.wikipedia.org/wiki/Dobutamine

Dobutamine is a direct-acting inotropic agent whose primary activity results from stimulation of the
receptors of the heart while producing comparatively mild chronotropic, hypertensive, arrhythmogenic,
and vasodilative effects. It does not cause the release of endogenous norepinephrine, as
does dopamine. In animal studies, dobutamine produces less increase in heart rate and less decrease in
peripheral vascular resistance for a given inotropic effect than does isoproterenol.
In patients with depressed cardiac function, both dobutamine and isoproterenol increase the cardiac
output to a similar degree. In the case of dobutamine, this increase is usually not accompanied by
marked increases in heart rate (although tachycardia is occasionally observed), and the cardiac stroke
volume is usually increased. In contrast, isoproterenol increases the cardiac index primarily by increasing
the heart rate while stroke volume changes little or declines.
Facilitation of atrioventricular conduction has been observed in human electrophysiologic studies and in
patients with atrial fibrillation.
Systemic vascular resistance is usually decreased with administration of dobutamine. Occasionally,
minimum vasoconstriction has been observed.
Most clinical experience with dobutamine is short-termnot more than several hours in duration. In the
limited number of patients who were studied for 24, 48, and 72 hours, a persistent increase in cardiac
output occurred in some, whereas output returned toward baseline values in others.
The onset of action of dobutamine is within 1 to 2 minutes; however, as much as 10 minutes may be
required to obtain the peak effect of a particular infusion rate.
The plasma half-life of dobutamine in humans is 2 minutes. The principal routes
of metabolism are methylation of the catechol and conjugation. In human urine, the major excretion
products are the conjugates of dobutamine and 3-O-methyl dobutamine. The 3-O-methyl derivative of
dobutamine is inactive.
Alteration of synaptic concentrations of catecholamines with either reserpine or tricyclic
antidepressants does not alter the actions of dobutamine in animals, which indicates that the actions of
dobutamine are not dependent on presynaptic mechanisms.
The effective infusion rate of dobutamine varies widely from patient to patient, and titration is always
necessary (see DOSAGE AND ADMINISTRATION). At least in pediatric patients, dobutamine-induced
increases in cardiac output and systemic pressure are generally seen, in any given patient, at lower
infusion rates than those that cause substantial tachycardia

Dobutamine is a direct-acting agent whose primary activity results from stimulation of the 1adrenoceptors of the heart, increasing contractility and cardiac output. Since it does not act
on dopamine receptors to induce the release of norepinephrine (another 1 agonist), dobutamine is less
prone to induce hypertension than is dopamine.
Dobutamine is predominantly a 1-adrenergic agonist, with weak 2 activity, and 1 selective activity,
although it is used clinically in cases of cardiogenic shock for its 1 inotropic effect in increasing heart
contractility and cardiac output. Dobutamine is administered as a racemic mixture consisting of both (+)
and () isomers; the (+) isomer is a potent 1 agonist and 1 antagonist, while the () isomer is an
[4]
1 agonist. The administration of the racemate results in the overall 1 agonism responsible for its
activity. (+)-Dobutamine also has mild 2 agonist activity, which makes it useful as a vasodilator
Dobutamine is a sympathomimetic amine that was designed as an inotropic agent for use in congestive heart
failure. Clinically, dobutamine increases cardiac output by selectively augmenting stroke volume, and this is
associated with a decrease in total peripheral vascular resistance that is mediated, in part, by reflex withdrawal of
sympathetic tone to the vasculature

8. Discuss the use of cefotaxime and doxycycline.

http://www.rxlist.com/cefotaxime-drug.htm
http://www.merckmanuals.com/professional/lexicomp/doxycycline.html

Cefotaxime (cefotaxime for injection) for Injection USP

and Dextrose Injection
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefotaxime
(cefotaxime for injection) for Injection USP and Dextrose Injection and other antibacterial drugs,
Cefotaxime (cefotaxime for injection) for Injection USP and Dextrose Injection should be used only to
treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Doxycycline
Pharmacologic Category
Antibiotic, Tetracycline Derivative
Pharmacologic Category Synonyms
Tetracycline Derivative Antibiotic
Use: Labeled Indications
Principally in the treatment of infections caused by susceptible Rickettsia, Chlamydia, andMycoplasma;
alternative to mefloquine for malaria prophylaxis; treatment for syphilis, uncomplicated Neisseria
gonorrhoeae, Listeria, Actinomyces israelii, and Clostridium infections in penicillin-allergic patients; used
for community-acquired pneumonia and other common infections due to susceptible organisms; anthrax
due to Bacillus anthracis, including inhalational anthrax (postexposure); treatment of infections caused by
uncommon susceptible gram-negative and gram-positive organisms including Borrelia

recurrentis, Ureaplasma urealyticum, Haemophilus ducreyi,Yersinia pestis, Francisella tularensis, Vibrio

cholerae, Campylobacter fetus, Brucella spp,Bartonella bacilliformis, and Klebsiella granulomatis, Q
fever, Lyme disease; treatment of inflammatory lesions associated with rosacea; intestinal amebiasis;
severe acne
Use: Dental
Treatment of periodontitis associated with presence of Actinobacillus actinomycetemcomitans(AA);
adjunct to scaling and root planing to promote attachment level gain and to reduce pocket depth in adult
periodontitis (systemic levels are subinhibitory against bacteria)
Use: Unlabeled/Investigational
Sclerosing agent for pleural effusion injection; vancomycin-resistant enterococci (VRE); alternate
treatment for MRSA infections; treatment of periodontitis (refractory); localized juvenile periodontitis (LIP)

9. Discuss the metabolism of Bilirubin.

http://en.wikipedia.org/wiki/Bilirubin#Metabolism

Overview of Bilirubin
Metabolism
The breakdown of heme
produces bilirubin (an insoluble waste
product) and other bile
pigments.Bilirubin must be made water
soluble to be excreted. This
transformation occurs in 5 steps:
formation, plasma transport, liver
uptake, conjugation, and biliary
excretion.
Formation: About 250 to 350 mg of
unconjugated bilirubin forms daily; 70
to 80% derives from the breakdown of
degenerating RBCs, and 20 to 30%
(early-labeled bilirubin) derives
primarily from other heme proteins in
the bone marrow and liver. Hb is
degraded to iron and biliverdin,

which is converted to bilirubin.

Plasma transport: Unconjugated
(indirect-reacting) bilirubin is not
water soluble and so is transported in
the plasma bound to albumin. It
cannot pass through the glomerular
membrane into the urine. Albumin
binding weakens under certain
conditions (eg, acidosis), and some
substances (eg, salicylates, certain
antibiotics) compete for the binding
sites.
Liver uptake: The liver takes
up bilirubin rapidly but does not take up
the attached serum albumin.
Conjugation: Unconjugated bilirubin in
the liver is conjugated to form
mainly bilirubindiglucuronide, or
conjugated (direct-reacting)bilirubin.
This reaction, catalyzed by the
microsomal enzyme glucuronyl
transferase, renders the bilirubin water
soluble.
Biliary excretion: Tiny canaliculi
formed by adjacent hepatocytes
progressively coalesce into ductules,
interlobular bile ducts, and larger
hepatic ducts. Outside the porta
hepatis, the main hepatic duct joins the
cystic duct from the gallbladder to form
the common bile duct, which drains
into the duodenum at the ampulla of
Vater.
Conjugated bilirubin is secreted into
the bile canaliculus with other bile
constituents. In the intestine, bacteria
metabolize bilirubin to form

urobilinogen, much of which is further

metabolized to stercobilins, which
render the stool brown. In complete
biliary obstruction, stools lose their
normal color and become light gray
(clay-colored stool). Some urobilinogen
is reabsorbed, extracted by
hepatocytes, and re-excreted in bile
(enterohepatic circulation). A small
amount is excreted in urine.
Because conjugated bilirubin is
excreted in urine and
unconjugated bilirubin is not, only
conjugated hyperbilirubinemia (eg,
due to hepatocellular or cholestatic
jaundice) causes bilirubinuria.

10. Discuss the control and prevention methods of Leptospirosis.

The

antibiotic doxycycline

can prevent leptospirosis. It is given to people who were exposed to the bacteria at the same time as
people who have been infected.

How can leptospirosis be prevented and controlled?

Because of the large number of serovars and infection sources and the wide differences in transmission
conditions, the control of leptospirosis is complicated and will depend on the local conditions. Control can
be achieved by controlling the reservoir or reducing infection in animal reservoir populations such
as dogs or livestock. Control of wild animals may be difficult. Preventive measures must be based on
knowledge of the groups at particular risk of infection and the local epidemiological factors.
Prevention and control should be targeted at :
(a) the infection source;
(b) the route of transmission between the infection source and the human host; or
(c) infection or disease in the human host.

How can the infection source be controlled?

It is important to establish what animal species are the infection sources in a particular area. Control
measures can then be targeted to the local reservoir species of animals.
Such measures include:
the reduction of certain animal reservoir populations, e.g. rats;
the separation of animal reservoirs from human habitations by means of fences and screens;
the immunization of dogs and livestock;
the removal of rubbish and keeping areas around human habitations clean;
encouraging people not to leave food around, especially in recreational areas where rats may be
present.

How can transmission be interrupted?

It is important to be aware of the risk factors for human infection and, if possible, the infection source.
Risk of infection is minimized by avoiding contact with animal urine, infected animals or an infected
environment. Where appropriate, protective clothing should be worn and wounds covered with
waterproof dressings to reduce the chance of infection if exposure is likely, e.g. occupational or
recreational exposure.

How can humans be protected?

Much depends on detailed knowledge of how, where and when humans may become infected in a
particular area. One possibility is to increase awareness of the disease among the population, risk groups
and health care providers, so that the disease can be recognized and treated as soon as possible.
Doxycycline has been reported to give some protection against infection and disease. In certain
countries, vaccines for humans are available, but it should be remembered that they may only provoke
immune responses to the serovars included in the vaccine.

How can humans be protected by immunization?

Immunization by means of vaccines seems to provide a certain degree of protection. Vaccines are, in
principle, suspensions of killed leptospires. Protection is largely serovar-specific. In areas where
many serovars are causing leptospirosis, a vaccine must consist of different serovars matching those
circulating locally. In some countries, where many serovars occur, vaccines consist of a mixture of a few
of the most prevalent. Protective antibodies are produced only against the serovars present in the
particular vaccine used. Commercial human vaccines have been produced in France and Cuba.
However, these vaccines do not induce long-term protection against infection and do not provide
cross-protective immunity against heterogenous leptospiral serovars.

Can animals be immunized?

Dogs, pigs and cattle can be immunized with vaccines consisting of suspensions of killed leptospires.
Protection is largely serovar-specific. Immunization may prevent disease but does not always prevent the
development of renal carriage.

Can pathogenic leptospires in the environment be

controlled?
Small areas, such as floors, can be cleaned and disinfected, but disinfecting large natural areas such as
lakes or rivers is not possible. Leptospires are sensitive to many environmental influences. They are
rapidly killed by disinfectants and desiccation. However, leptospires shed in animal urine can survive
in the environment for weeks to months under suitable conditions, e.g. in moist soil or surface water
with a neutral or slightly alkaline pH.

Is there a WHO Collaborating Centre for Research and

Training on Leptospirosis in the South-East Asia Region?
Yes. Indian Council of Medical Research (ICMR), the Government of India established a National
Leptospirosis Reference Center to carry out research on leptospirosis in Port Blair in 1999. It is interesting
that the first report of bacteriologically confirmed cases of leptospirosis originated from the Andaman
islands in 1931. The World Health Organization designated the National Leptospirosis Reference Centre,
Port Blair as a WHO Collaborating Centre for diagnosis, research, reference and training on leptospirosis.

11. Discuss the lab diagnosis of Lepto. (Microbiology)