Leptospirosis

Sung Chul Hwang Dept. of Pulmonary and Critical Care Medicine Ajou University School of Medicine

Leptospira

Scanning electron micrograph of Leptospira interrogans strain RGA. Two spirochetes bound to a 0.2 m filter. Strain RGAwas isolated in 1915 by Uhlenhuth and Fromme from the blood of a soldier in Belgium.
CDC/NCID/Rob Weyant rsw2@cdc.gov

Taxonomy
Order: Spirochaetaes
Family: Spirochaetaceae Genus: Treponema Borrelia

Family: Leptospiraceae Genus: Leptospira

General Overview of Spirochaetales

Gram-negative spirochetes

Spirochete from Greek for coiled hair Extremely thin and can be very long Tightly coiled helical cells with tapered ends Motile by periplasmic flagella (a.k.a., axial fibrils or endoflagella)

General Overview of Spirochaetales

Outer sheath encloses axial fibrils wrapped around protoplasmic cylinder
Axial fibrils originate from insertion pores at both poles of cell May overlap at center of cell in Treponema and Borrelia, but not in Leptospira Differering numbers of endoflagella according to genus & species

Periplasmic Flagella Diagram

Tightly Coiled Spirochete

OS = outer sheath AF = axial fibrils

AF

Leptospira interrogans

Cross-Section of Spirochete with Periplasmic Flagella

Cross section of Borrelia burgdorferi

NOTE: a.k.a., endoflagella, axial fibrils or axial filaments.

(Outer sheath)

Spirochaetales Associated Human Diseases

Genus Species Disease Syphilis Bejel Yaws Pinta Lyme disease (borreliosis) Epidemic relapsing fever Endemic relapsing fever Leptospirosis (Weils Disease)

Treponema

pallidum ssp. pallidum pallidum ssp. endemicum pallidum ssp. pertenue carateum burgdorferi recurrentis
Many species

Borrelia

Leptospira

interrogans

Introduction
Spirochetal disease, finely coiled, motile, 0.1 m x 6 20 m Systemic infection manifested as widespread vasculitis Zoonosis L. interogans 23 serogroups and 187 serovars L. biflexa : non-pathogenic, saprophyte

Epidemiology
Disease of the wild animals Incidental human infection by direct or indirect contact with the animal 20-40s active males: farmers or soldiers in harvest time 9-10 peak into November

Reservoires of Infection
Rats Dogs Live stocks Rodents including rabbits Wild animals Cats

Sources of Human Infections

Contaminated Water or soil from infected urine Direct animal contacts Occupational exposure : farmers, vets, abattoire workers Recreational exposure : campers, swimmers, visiting graveyards

Leptospirosis in Humans
Incubation period: 2-30 days, usually 5-14 days Broad spectrum of manifestations Acute undifferentiated fever Dengue-like syndrome (fever, headache, myalgia) Aseptic meningitis Weills disease (jaundice, renal failure, bleeding) Pulmonary hemorrhage syndrome

Case fatality rate is 5-40% >50% for pulmonary hemorrhage syndrome

Major cause of hemorrhagic fever
Albert Icksang Ko, MD

Routes of Infection
Contact with water or soil contaminated animals Direct contact with the by urine from infected source, farmer, vets, butchers, recreational activities Rodents carry EH fever, scrub typhus, paratyphus, leptospirosis Factors for high incidence : rain during harvest time, carrier rate in rodents Spirochetes survive longer in wet swampy conditions

Pathogenesis
Entry sites : skin wounds or abrasions in hand and feet and mucous membranes, conjunctiva, nasal, oral Bacteremia involving the entire body including eye, CSF Systemic effect and vasculitis due to endotoxin (hyaluronidase) and burrowing motility Hemorrhagic necrosis esp. in liver, lung, and kidneys jaundice, ARF, hemorrhages

Clinical types
Types Pneumonitis Rash type Weils disease Renal failure Flue-like Acute Hepatitis Combination 1986 33% 17% 15% 13% 15% 8% 1987 57.7%

53.8% 13.5% 86.5%

Phase I (Septicemic)
Following incubation period of 7-10 days High spiking fever, headaches, myalgia, arthralgias Lasting 4 7 days Proteinuria and increased creatinnine Organism detectable but serologic diagnosis not possible

Phase II (Immune)
Much more variable Induction of IgM Antibodies 1- 3 day freedom recurrence of symptoms Lower fever, CNS signs Maybe cultured from urine but not from blood or CSF

Weils Disease
Less common but severe form Mild phase I, initially Followed by severe Jaundice , Azotemia, and Hemorrhage from Lungs, GI tract, and other organs (3-6 day) Oliguric renal failure and Liver dysfunction dominate the clinical picture

Clinical Signs of Leptospirosis

Pulmonary infiltrates, pneumonitis, hemorrhages Conjunctival injection Jaundice Muscle tenderness Abdominal tenderness CVA tenderness Abnormal auscultation Erythema, petechiae, neck stiffness, adenopathy

Clinical Signs of Leptospirosis

Conjunctival injection/hemorrhage

Albert Icksang Ko, MD

Clinical Signs of Leptospirosis

Conjunctival injection/hemorrhage

Laboratory Diagnosis
Microbiologic identification : Blood or CSF first 10 days Urine second week (Fletchers, EMJH Medium) Serology: screeningMicroscopic Slide Agglutination (MST), titration & serogroup identification Microscopic Agglutination (MAT), detection of IgM (ELISA)

Barriers to Timely Identification and Treatment

Presentation of early-phase leptospirosis is non-specific. Misdiagnosis is common:
Dengue Malaria Scrub typhus

Misdiagnosis leads to poor outcomes (Am J Trop Med Hyg 2001;65:657):

Of these, 61% were diagnosed as dengue Associated with increased ICU admission (OR, 2.7 [0.8-9.5]) and mortality (OR, 5.1 [0.8-55.0]).

A Tarde, Salvador, June 1996

42% of leptospirosis cases sought care in the 1st three days of illness

Albert Icksang Ko, MD

Need for Rapid Diagnostics for Leptospirosis

Current serologic tests have <30-50% sensitivity during the 1st week of illness Lig proteins are immunodominant a ntigens (J Clin Microbiol 2007;45:1528)
Sensitivity and specificity >90-95%

Improved sensitivity (80%) during th e 1st week of illness.

Fiocruz-Cornell is developing a Lig -based lateral flow assay
Point-of-care diagnosis Clinical evaluation in 2009
Albert Icksang Ko, MD

Chest X-rays
33 64 % of patientssjows abnormality Bilateral nodules, rosette densities Diffuse ill-defined infiltrates Massive confluent consolidation Bilateral, Non-lobar, peripheral predominance Rare pleural reaction Complete resolution within 5 to 10 days

Differential Diagnosis
EH fever Rickettsial disease : Scrub typhus, murine typhus Acute viral hepatitis Sepsis Influenza Aseptic Meningitis

Treatment
Early anti-microbial therapy is importantshorten the course and prevent carrier state Choice : Penicillin G, Ampicillin May cause Jarish-Herxheimer type reaction Mild cases oral Doxycycline or Amoxicillin

Prevention
Vaccination of domestic animals Rodent control Protective gloves and boots Avoid swimming in contaminated waters Vaccination in endemic region

Control of Rodent Sources of Transmission

Reduce reservoir density Pesticides Deny access to human living environment Deny access to food and water Remove food sources and ecological habitats Limitations: Pesticides are costly. Rodent control can not be accomplished by chemical int erventions alone (recrudescence, pesticide resistance).

Albert Icksang Ko, MD

Prevent Exposures to Transmission Sources

Disinfecting areas of contaminated environment (h ypochlorite) Protective clothing (boots, gloves) Cleaning wounds after exposure Prevention of contact with ill or dead animals

Health education on risk exposures

Remove transmission sources

What good does it do to treat people's illnes ses ...

then send them back to the conditions that made them sick?
Michael Marmot, Commission of Social Determinants of Health, WHO