Leptospirosis

• Leptospirosis is an emerging infectious

disease of global importance
• clinical manifestations varying
• from inapparent infection to fulminant, fatal
disease.
• In its mild form, present as an influenza-like illness
• In severe leptospirosis, Weil's syndrome.
• In most countries, leptospirosis in humans
is an underestimated problem.
 Etiological Agent
• the genus Leptospira comprised two
species: the pathogenic L. interrogans and
the free-living L. biflexa
• The pathogenic leptospires are divided
into serovars according to their antigenic
composition. More than 250 serovars
make up the 26 serogroups.
 Epidemiology
• is an important zoonosis
• worldwide distribution
• affecting at least 160 mammalian species.
– Rodents, especially rats, are the most
important reservoir
– e.g. Icterohaemorrhagiae and Copenhageni
with rats, Grippotyphosa with voles, Hardjo
with cattle, Canicola with dogs, and Pomona
with pigs
 Transmission
• direct contact with urine, blood, or tissue
from an infected animal
• or exposure to a contaminated
environment;
• human-to-human transmission is rare.
• Since leptospires are excreted in the urine
and can survive in water for many months,
water is an important vehicle in their
transmission.
• In 1999, more than 500,000 cases were
reported from China, (Mortality 0.9 to
7.9%).
• In Brazil, more than 28,000 cases were
reported in the same year.
• In the United States, the 40–120 cases
reported annually to CDC
•
• Certain occupational groups are at especially
high risk;
– veterinarians,
– agricultural workers,
– sewage workers,
– slaughterhouse employees,
– workers in the fishing industry.
• Such individuals may acquire leptospirosis
through direct exposure to or contact with
contaminated water and soil.
• Recreational water activities, such as canoeing,
windsurfing, swimming, and waterskiing, place
persons at risk.
 Pathogenesis
• Leptospires enter the host through abrasions in the skin
or through intact mucous membranes, especially the
conjunctiva and the lining of the oro- and nasopharynx.
• Drinking of contaminated water may introduce
leptospires through the mouth, throat, or esophagus.
• After entry of the organisms, leptospiremia develops,
with subsequent spread to all organs
• All forms of leptospires can damage the wall of small
blood vessels; this damage leads to vasculitis with
leakage and extravasation of cells, including
hemorrhages.
 Clinical Manifestations
• The incubation period is usually 1–2 weeks but
ranges from 2 to 20 days
• Many Leptospira-infected persons remain
asymptomatic.
• In symptomatic cases, clinical manifestations vary
from mild to serious or even fatal.
– Anicteric form: seen in >90% of symptomatic persons
– Severe leptospirosis with profound jaundice (Weil's
syndrome): seen in 5–10% of individuals.
 Anicteric Leptospirosis
• present as an acute influenza-like illness,
• fever, chills, severe headache, nausea, vomiting, and
myalgias.
• Muscle pain, which especially affects the calves, back,
and abdomen, is an important feature of leptospiral
infection.
• Less common features include sore throat and rash.
• The patient usually has an intense headache (frontal or
retroorbital)
• sometimes develops photophobia, mental confusion.
• Pulmonary involvement, manifested in most cases by
cough and chest pain and in a few cases by hemoptysis.
• The most common finding on physical examination
– fever with conjunctival suffusion.
– muscle tenderness, lymphadenopathy, pharyngeal injection,
rash, hepatomegaly, and splenomegaly.
– The rash may be macular, maculopapular, erythematous,
urticarial, or hemorrhagic. Mild jaundice may be present.
• Most patients become asymptomatic within 1 week.
• After an interval of 1–3 days, the illness recurs in a
number of cases.
• The start of this second (immune) phase coincides with
the development of antibodies.
• Often the fever and myalgias is less pronounced.
• aseptic meningitis ~15%
Severe Leptospirosis (Weil's Syndrome)

• is characterized by jaundice, renal dysfunction, and

hemorrhagic diathesis; by pulmonary involvement
in many cases; and by mortality rates of 5–15%.
• this syndrome is frequently seen with infection due
to serovar Icterohaemorrhagiae/Copenhageni.
• Rhabdomyolysis, hemolysis, myocarditis,
pericarditis, congestive heart failure, cardiogenic
shock, adult respiratory distress syndrome,
necrotizing pancreatitis, and multiorgan failure have
all been described during severe leptospirosis.
• Leptospirosis should be differentiated from
other febrile illnesses associated with
headache and muscle pain, such as
dengue, malaria, enteric fever, viral
hepatitis, Hantavirus infections, and
rickettsial diseases.
Laboratory and Radiologic Findings
• WBC count 3000 to 26,000/ L, with a left shift;
• in Weil's syndrome, leukocytosis is often marked.
• Mild thrombocytopenia in up to 50% of patients
• ESR elevated.
• LFT
– elevated serum levels of bilirubin
– alkaline phosphatase
– mild increases (up to 200 U/L) in serum levels of
aminotransferases.
– Prolonged PT
• CXR
• CSF
• A definite diagnosis of leptospirosis
– isolation of the organism from the patient
– or on seroconversion
– or a rise in antibody titer in the microscopic
agglutination test (MAT).
– ELISA
– These rapid tests, latex agglutination test, or ELISA
methodology
– Cultures: Ellinghausen-McCullough-Johnson-Harris
(EMJH) medium
 Treatment
• Treatment should be initiated as early as
possible.
• In milder cases, oral treatment with tetracycline,
doxycycline, ampicillin, or amoxicillin should be
considered.
• For severe cases of, intravenous administration
of penicillin G, amoxicillin, ampicillin, ceftriaxone,
cefotaxime or erythromycin is recommended .
• In rare cases, a Jarisch-Herxheimer reaction
develops within hours after the start of
antimicrobial therapy
 Meningococcenia
• Neisseria meningitidis is the etiologic agent of
two life-threatening diseases:
– meningococcal meningitis
– fulminant meningococcemia.
• Meningococci are gram-negative aerobic
diplococci and have a polysaccharide capsule.
• transmitted among via respiratory secretions.
• Colonization of the nasopharynx or pharynx is
much more common than invasive disease.
• Meningococci are classified into
serogroups according to the antigenicity of
their capsular polysaccharides.
• Five serogroups (A, B, C, Y, and W-135)
are responsible for >90% of cases of
meningococcal disease worldwide.
• Epidemiology
• Meningococcal disease occurs worldwide as
isolated (sporadic) cases, institution- or community-
based outbreaks, and large epidemics.
• N. meningitidis is still a leading global cause of
meningitis and rapidly fatal sepsis, often in
otherwise-healthy individuals.
• Serogroup A strains, which caused most of the
large epidemics of meningococcal disease
 Pathogenesis
• Meningococci that colonize the upper respiratory
tract are internalized by nonciliated mucosal cells
and may traverse them to enter the submucosa,
from which they can make their way into the
bloodstream.
– Fulminant Meningococcemia: 15%
– Meningitis + Meningococcemia: 30%
– Meningitis: 55%
 Clinical Manifestations

• Upper Respiratory Tract Infections

• Meningococcemia
• Meningitis
• Other Manifestations
 Meningococcemia
• fever, chills, nausea, vomiting, and myalgias.
• Prostration is common.
• The most distinctive feature is rash.
– Erythematous macules rapidly become petechial and, in severe
cases, purpuric.
– the lesions are typically found on the trunk and lower extremities,
they may also occur on the face, arms, and mucous
membranes.
– The petechiae may coalesce into hemorrhagic bullae or may
undergo necrosis and ulcerate.
– Patients with severe coagulopathy may develop ischemic
extremities or digits, often with a sharp line of demarcation
between normal and ischemic tissue.
• The Waterhouse-Friderichsen syndrome is a dramatic
example of DIC-induced microthrombosis, hemorrhage,
and tissue injury.
• Meningitis
• Other Manifestations
– Arthritis occurs in ~10% of patients with
meningococcal disease.
– Meningococcal pneumonia
– meningococcal pericarditis
– Primary meningococcal conjunctivitis
– meningococcal urethritis
 Diagnosis
• The definitive diagnosis is established by recovering N.
meningitidis, its antigens, or its DNA from normally sterile
body fluids (e.g., blood, CSF, or synovial fluid) or from
skin lesions.
• Meningococci grow best on Mueller-Hinton or chocolate
blood agar
• A Gram's stain of CSF reveals intra- or extracellular
organisms in ~85% of patients with meningococcal
meningitis.
• The latex agglutination test
• PCR amplification of DNA in buffy coat or CSF samples
 Treatment
– 1. Ceftriaxone 2 g IV q12h (100 mg/kg per day) or cefotaxime 2
g IV q4h
– 2. For penicillin-sensitive N. meningitidis: Penicillin G 18–24
million units per day in divided doses q4h (250,000 units/kg per
day)
– 3. Chloramphenicol 75–100 mg/kg per day in divided doses q6h
– 4. Meropenem 1.0 g (children, 40 mg) IV q8h
– 5. In an outbreak setting in developing countries: Long-acting
chloramphenicol in oil suspension (Tifomycin), single dose
• Adults: 3.0 g (6 mL)
• Children 1–15 years old: 100 mg/kg
• Children <1 year old: 50 mg/kg
 Chemoprophylaxis
– Rifampin (oral)
• Adults: 600 mg bid for 2 days
• Children 1 month old: 10 mg/kg bid for 2 days
• Children <1 month old: 5 mg/kg bid for 2 days
– Ciprofloxacin (oral)
• Adults: 500 mg, 1 dose
– Ofloxacin (oral)
• Adults: 400 mg, 1 dose
– Ceftriaxone (IM)
• Adults: 250 mg, 1 dose
• Children <15 years old: 125 mg, 1 dose
– Azithromycin (oral)
• 500 mg, 1 dose
 Vaccination
• Vaccinationc A, C, Y, W-135 vaccine
(Memomune, Aventis Pasteur)
• or
• A, C vaccine Single 0.5-mL subcutaneous
injection
• New C; A, C; and A, C, Y, W-135
meningococcal conjugate vaccines
 Brucellosis
• Brucellosis is a bacterial zoonosis
• brucellae are small, gram-negative, unencapsulated,
nonsporulating rods or coccobacilli
• The nomen system recognizes
– B. melitensis, which is the commonest cause of symptomatic
disease in humans and for which the main sources are sheep,
goats, and camels
– B. abortus, which is usually acquired from cattle or buffalo
– B. suis, which generally is acquired from swine
– B. canis, which is acquired most often from dogs.
– B. ovis, which causes reproductive disease in sheep, and
– B. neotomae, which is specific for desert rodents, have not been
clearly implicated in human disease..
• Human brucellosis is usually associated with
occupational or domestic exposure to infected
animals or their products.
– Farmers, shepherds, goatherds, veterinarians, and
employees in slaughterhouses and meat-processing
plants.
– Dairy products, especially soft cheeses, unpasteurized
milk, and ice cream, are the most frequently implicated
sources of infection; raw meat and bone marrow may be
sources under exceptional circumstances
• Brucellosis may be acquired by ingestion,
inhalation, or mucosal or percutaneous exposure.
 Clinical Features
• fever, which may be associated with
profuse sweats, especially at night.
(1) Left untreated, the fever of brucellosis
shows an undulating pattern that persists for
weeks before the commencement of an
afebrile period that may be followed by
relapse.
(2) The fever of brucellosis is associated with
musculoskeletal symptoms and signs in
about one-half of all patients.
• lose appetite and weight; nonspecific myalgia,
headache, and chills.
• the presentation of brucellosis often fits one of
three patterns:
– febrile illness that resembles typhoid but is less
severe
– fever and acute monoarthritis, typically of the hip or
knee, in a young child
– and long-lasting fever, misery, and low-back or hip
pain in an older man.
• Osteomyelitis more commonly involves
– the lumbar and low thoracic vertebrae than
the cervical and high thoracic spine.
• Individual joints that are most commonly
affected
– are the knee, hip, sacroiliac, shoulder, and
sternoclavicular joints
– the pattern may be one of monoarthritis or
polyarthritis.
• dry cough
• chest x-ray, although pneumonia, empyema,
intrathoracic adenopathy, or lung abscess can
occur.
• One-quarter of patients have
hepatosplenomegaly, and 10–20% have
significant lymphadenopathy
• Neurologic involvement is common
• Endocarditis occurs in ~1% of cases
 Diagnosis
• clinical picture of brucellosis is not distinctive, the
diagnosis must be based on a history of potential
exposure, a presentation consistent with the disease, and
supporting laboratory findings.
• Blood inv
• standard agglutination test (SAT) is still the mainstay of
serologic diagnosis
• Isolation of bacteria: Isolation of brucellae from blood,
CSF, bone marrow, or joint fluid or from a tissue aspirate
or biopsy sample is definitive, and attempts at isolation are
usually successful in 50–70% of cases.
• Biopsied samples of tissues such as lymph node or liver
may show noncaseating granulomas
 Treatment
• streptomycin monotherapy showed that relapse was
common; thus dual therapy with tetracyclines became
the norm
• "gold standard" for the treatment of brucellosis in adults
is IM streptomycin (0.75–1 g daily for 14–21 days)
together with doxycycline (100 mg twice daily for 6
weeks).
• rifampin (600–900 mg/d) plus doxycycline (100 mg twice
daily) for 6 weeks.
• ofloxacin (400 mg twice daily) or ciprofloxacin (500 mg
twice daily), given together with rifampin for 6 weeks,
may become accepted as an alternative to the other 6-
week regimens for adults
• For adults with acute nonfocal brucellosis (duration, <1
month),
– a 6-week course of therapy incorporating at least two
antimicrobial agents is required.
• Complex or focal disease necessitates 3 months of
therapy.