2017 Kesling Sesi 8 TW Rodent Borne Diseases

Rodent-Borne Diseases
Tri Wibawa
Department of Microbiology
FM - UGM

Rodents-Borne Diseases
• Rodents are among the most abundant of wild
animal hosts of zoonoses
• Diseases:
– Hantavirus infection
– leptospirosis
– bartonellosis
– Plague
– Ricketsioses

(Bordes et al., 2015)`

(Meerburg, 2009)

ENSO= El Nino Southern Oscillation

(WHO, 2003)

(WHO, 2003)

(WHO, 2003)

LEPTOSPIROSIS

Examples of Diseases Whose Health Impacts have been
Influenced by Urbanization and Urban Poverty
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Hypertension
Obesity
Asthma
Occupational diseases
Violence
Dengue
Visceral leishmaniasis
Tuberculosis
Bacterial meningitis
Acute rheumatic fever
Leptospirosis

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Leptospirosis
• Leptospirosis is a systemic disease of humans
and domestic animals, mainly dogs, cattle and

swine
• Characterized by
– Fever
– renal and hepatic insufficiency,
– pulmonary manifestations
– reproductive failure
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Global Burden and Epidemiology of
Leptospirosis
• 500,000 reported cases each year (WHO. Weekly
Epid Rec. 1999;74:237-242)

• Burden underestimated due to misdiagnosis
and lack of effective diagnostic tests
• Traditionally, sporadic occupation-related
disease
– Veterinarians, abattoir workers, domestic animal
herders

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Global Total Burden of Leptospirosis

(Torgerson et al., 2015)

• Rural-based subsistence farming
– Wet-land farming (i.e. rice harvesting)
– Dry-land farming (i.e. sugar cane)
– Ubiquitous environmental exposures

• The incidence is significantly higher in
warmclimate countries than in temperate
regions

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Leptospirosis Causative Agent
• Spirochete
• Genus Leptospira (Adler et al, 2010)

– 13 pathogenic Leptospira species: L. alexanderi, L. alstonii
(genomospecies 1), L. borgpetersenii, L. inadai, L. interrogans, L.
fainei, L. kirschneri, L. licerasiae, L. noguchi, L. santarosai, L.
terpstrae (genomospecies 3), L. weilii, L. Wolffii  with > 260
serovars
– Saprophytic species of Leptospira include: L. biflexa, L. meyeri, L.
yanagawae (genomospecies 5), L. kmetyi, L. vanthielii
(genomospecies 4), and L. wolbachii
 > 60 serovars

• 6-20 µm x 0.1 µm
• Highly motile

– Periplasmic flagella

• Survives in environment weeks to months

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Leptospira Classification
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Phenotypic/Serologic: (prior 1989)

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Genotypic:

– L. interrogans  pathogenic strains
– L. biflexa  saprophytic strains
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L. interrogans
L. noguchii
L. santarosai
L. meyeri
L. wolbachii
L. biflexa
L. fainei
L. borgpetersenii
L. kirschneri
L. weilii
L. inadai
L. parva

L. alexanderi

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Leptospira and Leptospirosis
• Tight, regular individual coils with a bend or hook at
one or both ends
• L. biflexa – harmless, free-living saprobe
• L. interrogans – causes leptospirosis, a zoonosis
– bacteria shed in urine; infection occurs by contact with
contaminated urine; targets kidneys, liver, brain, eyes
– sudden high fever, chills, headache, muscle aches,
conjunctivitis, and vomiting
– Long term infections may affect kidneys and liver.

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Transmission and Pathogenesis of

Leptospirosis
• The most widespread zoonosis
• Persistent colonization and shedding from renal tubules
• Transmission:

– Direct contact with reservoir
– Indirect contact with an environment contaminated with reservoir
urine
– Animal bite  rare
– Human-human ?? (sexual intercourse, breast feeding)

• Penetrate mucous membranes and breaks in skin
• Rapid dissemination and trophism to kidneys of reservoir
hosts
• Tissue damage in susceptible hosts (immunopathogenic or
toxin mediated process)
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Scanning electron microscopy of a renal tubule from

an experimentally infected rat

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Leptospirosis in Humans
• Incubation period: 2-30 days, usually 5-14 days
• Broad spectrum of manifestations
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Acute undifferentiated fever
Influanza-like syndrome (fever, headache, myalgia)
Aseptic meningitis (≤ 25% of all ases
Weill’s disease jaundi e, renal failure, leeding,
myocarditis)
– Pulmonary hemorrhage respirtory failure

• Case fatality rate is 5-40%

– >50% for pulmonary hemorrhage syndrome

• Major cause of hemorrhagic fever
• intrauterine infection and fetal death
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Leptospira Morbidity
• This is not clear.
• Leptospirosis may be underdiagnosed
because:
– The diagnosis is difficult to confirm;
– It may be confused with other diseases;
– The disease may be mild and not be investigated
in the laboratory.

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Clinical Manifestation in Human
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Febrile illness
Headache
Myalgia
Abdominal pain,
conjunctival suffusion
skin rash
Cough
Dyspnea
hemoptysis
adult respiratory distress syndrome
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Organs Involves
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Kidney
Liver
Skin
Brain
Muscle
Eyes

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Differential Diagnosis
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Common viral infections, such as influenza
Human immunodeficiency virus seroconversion
Dengue
Fever of unknown origin
Typhoid.
Encephalitis
Poliomyelitis
Rickettsiosis
Glandular fever
(infectious mononucleosis),
Brucellosis,
Malaria,
Viral hepatitis,
Pneumonitis.
Hantavirus infections

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Leptospirosis Treatment
• Doxycycline (100 mg twice daily for 7 days)
• Penicillin (amoxicillin, ampicillin)
• Other choice: erythromycin, ceftriaxone and
cefotaxime
• Prophylaxis:
– Doxycycline (200 mg orally, once weekly)
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CONTROL OF LEPTOSPIROSIS
• At the source of infection
– Reservoir host
– Carrier
– Shedder

• At the transmission route
• At the level of the human host

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Prevent Exposures to
Transmission Sources
• Disinfecting areas of
contaminated environment
(hypochlorite)
• Protective clothing (boots, gloves)
• Cleaning wounds after exposure
• Prevention of contact with ill or dead animals
• Health education on risk exposures
• Remove transmission sources
• Inhibited at low detergent concentrations

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Reservoirs
• Mice

– (Mus musculus and other Mus species)

• Rats

– mainly Rattus norvegicus and R. rattus

• Host-related serovars
– Mice

• Ballum
• Icterohaemorrhagiae

– Rats for Copenhageni

• Different rodent species may be reservoirs of distinct
serovars.
• They usually do not show signs, but harbor leptospires in
their kidneys, becoming an important source of infection
for humans or other animals  shed the organisms in their
urine for their lifetime
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• Culturing of kidney tissues  the most reliable
method of detecting infection in animals.
• Rodent surveys require live-trapped animals
• Swine and cattle may be conducted at abattoirs after
the animals are killed
• Culture of urine from live domestic animals 
difficult and samples easily become contaminated.

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Can the Environment be Checked for
Pathogenic Leptospires?
• Detection
– Culture

• Samples of water and soil can be cultured and checked
for growth of pathogenic leptospires  Need long time

– PCR
– Animal Inoculation

• Negative results do not exclude the presence
of pathogenic leptospires in the environment

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Diagnosis of Leptospirosis
• Specimens
– Blood in a heparin tube
– Cerebrospinal fluid
– Tissues microscopic examination and culture.
– Urine
– Serum for agglutination tests.

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Methods for Diagnosis of Leptospirosis
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Microscopic Examination
Culture
Serology (IgG/IgM/MAT)
Molecular method (PCR based)

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RICKETTSIOSES

Rickettsioses
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Acute febrile
Zoonotic diseases caused by rickettsiae,
Obligate intracellular Gram-negative bacteria
Invade endothelial cells and induce the formation of
vasculitis.
• Vectors: various arthropods, including lice, fleas,
ticks, and mites,
• mammals and sometimes the arthropods them
selves constitute the principal reservoirs
• Eighteen rickettsioses, divided into 3 biogroups

Rickettsioses

(Jensenius et al, Clin Infect Dis 2004; 39:1493–9)

(Jensenius et al, Clin Infect Dis 2004; 39:1493–9)

Rickettsioses
• Diagnosis

– Culture
– PCR
– Serology (IFAT) – most aplicable

• Treatment

– Doxycycline
– Chloramphenicol
– Other macrolites

• Prevention

– Avoid exposure
– Repellent for the vectors
– No vaccination available

PLAGUE

Plague
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Caused by the bacteria Yersinia pestis
A zoonotic bacteria
Usually found in small mammals and their fleas.
It is transmitted between animals from their fleas.
From 2010 to 2015 there were 3248 cases reported
worldwide, including 584 deaths.
• Humans can be contaminated by
– the bite of infected fleas
– through direct contact with infected materials
– inhalation.

Countries Having Notified Human Plaque to WHO 2002 - 2015

https://www.economist.com/blogs/graphicdetail/2017/07/daily-chart-1

• Y pestis exists as an obligate parasite and has a
limited ability to survive outside an infected
mammal
• It is non–spore forming
• Sensitive to sunlight and heating
• Can not survive long in environment  plague
aerosol would be infectious for as long as 1
hour in a worst-case scenario
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• incubation period of one to seven days.
• Case-fatality ratio of 30%-100% if left untreated.
• Two main clinical forms of plague infection:
– Bubonic
• the most common form
• characterized by painful swollen lymph nodes or 'buboes'.

– Septicemic
– Pneumonic.

Laboratory Diagnosis
• Specimen: blood, aspirates from involved lymph
nodes, skin scrapings, cerebrospinal fluid, urine,
and sputum.
• Y pestis identification :
– Bacteriologic : Microscopic and culture
– Serologic methods:
• Detection of capsular antigen F1  expressed only at 37°C
• IHC, Immunofluorescence, ELISA

HANTA VIRUS INFECTION

Hantavirus
• Bunyaviridae family
• May cause hantavirus pulmonary syndrome (HPS), a serious
respiratory disease.
• Hantavirus pulmonary syndrome
– respiratory distress

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• pulmonary edema
• cough

fever
myalgias
nausea/vomiting
elevated WBC, RBC
T hrombocytopenia
hypotension

• mortality = 50%

A micrographic study of liver tissue seen from a Hantavirus
pulmonary syndrome (HPS) patient seen in this undated photo
obtained by Reuters, July 6, 2017. Centers for Disease Control
and Prevention/Handout via REUTERS

Hantavirus Transmission