Zoonotic diseases Meral Sönmezoğlu, Assoc Prof Infectious Diseases Department Yeditepe University Hospital.

ZoonoZoonotic tic diseases diseases ZoonoZoonotic tic diseases diseases

Meral Sönmezoğlu, Assoc Prof

Infectious Diseases Department

Yeditepe University Hospital

ZoonosesZoonoses

From the Greek:

Zoon: Animal

Noson: Disease

Diseases and infections which are naturally transmitted between vertebrate animals and humans

- WHO 1959

• 1. Know the general terminology and main organisms

• 2. Know epidemiology and clinical symptoms of main zoonotic diseases

• 3. Understand the importance of the diseases

Learning objectsLearning objects

DefinitionDefinition

• Zoonosis are diseases of vertebrate animals that can be transmitted to man: either directly or indirectly through an insect vector.

• Zoonosis are a complex group of diseases caused by a remarkable diversity of pathogenic microorganisms that ordinarily reside and cause illness in the nonhuman animal world

Defining criteriaDefining criteria

introduction to the zoonosis include the following:

• a vertebrate reservoir exclusive of humans; • transmission of the agent directly to people or

from products derived from the host animal or through an arthropod intermediate;

• and a recognized infectious disease syndrome in susceptible individuals

Zoonosis: ImportanceZoonosis: Importance

– In addition to their natural occurrence many of these microorganisms are prime candidates as biological weapons

Human Health

Animal Health

ZOONOSIS

Zoonosis (Zoonotic Diseases) - all diseases naturally transmissible from animals to man

ZoonosesZoonoses

• Does NOT include

– Fish and reptile toxins

– Allergies to vertebrates

– Diseases in which animal-derived food serves as a vehicle (e.g. hepatitis A contaminated deli meat)

– Experimentally transmitted diseases

ZoonosesZoonoses

• > 250 zoonotic diseases

• Multiple pets in the home

• Human-animal bond

• Exotic species as pets

Zoonoses: Common DiseasesZoonoses: Common Diseases

Frequency – (CDC, 2003)

Salmonella 39,919

Lyme disease 18,991

West Nile (CNS) 2,862

Trichinosis 4

ZoonosesZoonoses

• Zoonotic diseases can be severe, life threatening, and contagious

• and can even warn of an emerging epidemic or

• a possible bioterror act

ZoonosesZoonoses

Spectrum of Disease Severity

Death = rabies

Severe illness = plague

Chronic illness = Q-fever

Mild illness = psittacosis

Zoonoses: ImportanceZoonoses: Importance• Economics

– Zoonotic disease are expensive• Rabies post-exposure prophylaxis

• GI illness due to Salmonella or Campylobacter – lost productivity, medical costs

– Import/Export• BSE – restriction on cattle

• Avian Influenza – restriction on chicken

• Travel/Globalization• Decreased transit time - SARS

• Remote area accessibility

Zoonoses: Etiologic Classification

Zoonoses: Etiologic Classification

• Viral

• Bacterial

• Parasitic

• Mycotic

Zoonoses: Viral ExamplesZoonoses: Viral Examples

Colorado tick fever Japanese encephalitis

Ebola Monkeypox

Equine encephalitides (WEE, EEE, VEE)

Nipah

Hantaviruses Rabies

Hendra Rift Valley fever

Herpesvirus B West Nile virus

Influenza Yellow fever

Zoonoses: Bacterial ExamplesZoonoses: Bacterial Examples

Anthrax Plague

Brucellosis Psittacosis

Campylobacteriosis Q fever

Cat-scratch disease Relapsing fevers

Leptospirosis Salmonellosis

Listeriosis Tularemia

Lyme disease Yersiniosis

Zoonoses: Parasitic ExamplesZoonoses: Parasitic Examples

PROTOZOAL HELMINTHIC

Trypanosomiasis Baylisascariasis

Babesiosis Cysticercosis

Cryptosporidiosis Hydatidosis

Leishmaniasis Schistosome dermatitis

Giardiasis Trichinosis

Toxoplasmosis Visceral larva migrans and toxocariasis

Zoonoses: Mycotic ExamplesZoonoses: Mycotic Examples

Aspergillosis

Blastomycosis

Cryptococcosis

Dermatophytosis

Histoplasmosis

Sporotrichosis

Zoonoses: Animal SpeciesZoonoses: Animal Species

• Dogs & Cats– Rabies– Roundworm– Ringworm – Lyme Disease (dogs only)– Cat Scratch Disease (cats only)

• Food Animals– Salmonella– E.coli– Brucellosis

Zoonoses: Animal SpeciesZoonoses: Animal Species

• Birds: – Psittacosis– West Nile– Cryptococcus

• Reptiles, Fish, & Amphibians– Salmonella– Mycobacterium

• Wild Animals– Hantavirus– Plague– Tularemia

Routes of TransmissionRoutes of Transmission

• Direct– Droplet or Aerosol– Oral – Contact

• Indirect – Foodborne– Water-borne– Fomite– Vector-borne– Environmental

Routes of TransmissionRoutes of Transmission

• direct contact,

• ingestion,

• inhalation,

• arthropod intermediates,

• animal bites.

Dunne - CIDP January 18, 2005

Zoonoses - Life CycleZoonoses - Life Cycle

ORTHOZOONOSES

– May be perpetuated in nature by a

single vertebrate species

– E.g. rabies, brucellosis, anthrax

Dunne - CIDP January 18, 2005

Zoonosis: Rabies Life CycleZoonosis: Rabies Life CycleVirus inoculation (bite)

Salivary gland excretion

Zoonoses - Maintenance CycleZoonoses - Maintenance Cycle

CYCLOZOONOSES

– Requires more than one vertebrate species but no invertebrate host

– Most are cestodiases (tapeworm diseases)

• Taenia saginata and T. solium require man to be one of vertebrate hosts

• Others, such as hydatidosis, man is accidentally involved

Life Cycle:

Zoonoses - Life CycleZoonoses - Life Cycle

METAZOONOSES– Require both vertebrates and

invertebrates to complete transmission– All arboviral infections

• West Nile virus, Saint Louis encephalitis

– Some bacterial diseases• Plague, many rickettsia

– Some parasitic diseases• Leishmaniasis, schistosomiasis

Zoonoses: MetazoonosesZoonoses: Metazoonoses• Invertebrate Host: Mosquitoes

• Vertebrate Host: Birds

• Incidental Hosts: – HUMANS, horses, amphibians, other mammals

Risk FactorsRisk Factors

• Companion Animal – Dogs & roundworm

– Rats & Rat Bite Fever

• Occupational – Animal control workers & rabies

– Wildlife biologists & hantavirus

• Foodborne – Raw meat & E.coli

– Unpasteurized dairy & Listeria

Risk FactorsRisk Factors

• Recreational Activities

– Camping & Lyme disease

• Farm Settings

– Sheep & Q-fever

– Cattle & Cryptosporidium

• Travel

– Malaysia & Nipha

– Australia & Hendra

Reportable Diseases of Animals

Reportable Diseases of Animals

• By veterinarian or other individual• Reported to Health Services

– Plague – Rabies

• Reportable to Dept Food and Agriculture – Anthrax– Brucellosis– Glanders– Listeriosis– Rabies in livestock– Venezuelan equine encephalomyelitis– West Nile– And more…

RABIESRABIES

Dunne - CIDP January 18, 2005

Rabies VirusRabies Virus

• member of the Lyssavirus of the Rhabdoviridae.

• ssRNA enveloped virus, characteristic bullet-shaped appearance with 6-7 nm spike projections.

• virion 130-240nm * 80nm

• -ve stranded RNA codes for 5 proteins; G, M, N, L, S

• Exceedingly wide range of hosts.

• There are 5 other members of Lyssavirus : Mokola, Lagosbat, Duvenhage, EBL-1, and EBL-2.

• Duvenhage and EBL-2 have been associated with human rabies.

Rabies VirusRabies Virus

Structure of rabies virus (Source: CDC)

Rabies virus particles

DEFINITIONDEFINITION

• Rabies is an acute, progressive encephalomyelitis

• The case to fatality rate is the highest of any infectious disease

• One of the oldest described diseases

• The leading viral zoonosis as regards global public health significance

EpidemiologyEpidemiology

Rabies is a zoonosis which is prevalent in wildlife. The main animals involved differs from continent to continent. 

Europe fox, bats

Middle East wolf, dog

Asia dog

Africa dog, mongoose, antelope

N America foxes, skunks, raccoons, insectivorous bats

S America dog, vampire bats

DISTRIBUTIONDISTRIBUTION• Rabies is distributed on all

continents (with the exception of Antarctica)

• Several areas are considered ‘free’ of the disease, including many islands in Pacific Oceania

• Globalization may threaten the disease-free status of many localities, due to the introduction of rabid animals

BURDENBURDEN

• More than ~55,000 human rabies deaths per year

• Most occur in developing countries

• Millions of human exposures per year

• The domestic dog is the single most important animal reservoir (>99%)

• Wildlife important, especially in developed countries

RABIES PATHOGENESISRABIES PATHOGENESIS• Virus is transmitted via bite

• Agents are highly neurotropic

• Enter peripheral nerves

• Centripetal travel by retrograde flow in axoplasm of nerves to CNS

• Replicate in brain

• Centrifugal flow to innervated organs, including the portal of exit, the salivary glands

• Viral excretion in saliva

PathogenesisPathogenesis

• The commonest mode of transmission in man is by the bite of a rabid animal, usually a dog. Rabies is an acute infection of the CNS which is almost invariably fatal.

• Following inoculation, the virus replicates in the striated or connective tissue at the site of inoculation and enters the peripheral nerves through the neuromuscular junction.

• It then spreads to the CNS in the endoneurium of the Schwann cells.

• Terminally, there is widespread CNS involvement but few neurons infected with the virus show structural abnormalities. The nature of the profound disorder is still not understood.

CLINICAL STAGESCLINICAL STAGES

• Incubation Period (range = ~<7 days to >6 years; average is ~4-6 weeks)

• Prodromal Phase (Non-specific signs)

• Acute Neurological Phase

• Coma

• Death (recovery from rabies?)

RABIES RECOVERY?RABIES RECOVERY?

• Five historical human case recoveries, after vaccination, but before illness onset

• Only one documented unvaccinated human survivor after clinical presentation

RABIES DIAGNOSISRABIES DIAGNOSIS

• Based upon history of animal exposure and typical neurological clinical signs

• Postmortem demonstration of viral antigen in CNS is gold standard

• In humans, antemortem detection of virus or viral amplicons, antibodies, or antigens (sera, csf, saliva, nuchal biopsy)

Laboratory DiagnosisLaboratory Diagnosis

• Histopathology - Negri bodies are pathognomonic of rabies. However, Negri bodies are only present in 71% of cases.

• Rapid virus antigen detection - in recent years, virus antigen detection by IF had become widely used. Corneal impressions or neck skin biopsy are taken. The Direct Fluorescent Antibody test (DFA) is commonly used.

• Virus cultivation - The most definitive means of diagnosis is by virus cultivation from saliva and infected tissue. Cell cultures may be used or more commonly, the specimen is inoculated intracerebrally into infant mice.  Because of the difficulties involved, this is rarely offered by diagnostic laboratories.

• Serology - circulating antibodies appear slowly in the course of infection but they are usually present by the time of onset of clinical symptoms.  

Negri Body in neuron cell (source: CDC)

Positive DFA test (Source: CDC

Diagnosis of Rabies

PROPHYLAXISPROPHYLAXIS

• Pre-exposure Vaccination

• Postexposure Prophylaxis (PEP)

Management and Prevention

Management and Prevention

• Pre-exposure prophylaxis - Inactivated rabies vaccine may be administered to persons at increased risk of being exposed to rabies e.g. vets, animal handlers, laboratory workers etc.

• Post-exposure prophylaxis - In cases of animal bites, dogs and cats in a rabies endemic area should be held for 10 days for observation. If signs develop, they should be killed and their tissue.

• Wild animals are not observed but if captured, the animal should be killed and examined. The essential components of postexposure prophylaxis are the local treatment of wounds and active and passive immunization.

• Once rabies is established, there is nothing much that could be done except intensive supportive care. To date, only 2 persons with proven rabies have survived.

Postexposure ProphylaxisPostexposure Prophylaxis

• Wound treatment - surgical debridement should be carried out. Experimentally, the incidence of rabies in animals can be reduced by local treatment alone.

• Passive immunization - human rabies immunoglobulin around the area of the wound; to be supplemented with an i.m. dose to confer short term protection.

• Active immunization - the human diploid cell vaccine is the best preparation available. The vaccine is usually administered into the deltoid region, and 5 doses are usually given.

• There is convincing evidence that combined treatment with rabies immunoglobulin and active immunization is much more effective than active immunization alone. Equine rabies immunoglobulin (ERIG) is available in many countries and is considerably cheaper than HRIG.

RABIES BIOLOGICALSRABIES BIOLOGICALS

• Rabies Vaccines (for pre- and PEP)

• Rabies immune globulin (only in PEP)

PRE-EXPOSURE VACCINATION

PRE-EXPOSURE VACCINATION

• Vaccine given on days 0, 7, and 21 or 28

• Serology occurs every 6 months to 2 years (if remaining at risk)

• If antibody titer not adequate, administer a single booster dose

• If ever exposed, give a vaccine dose on days 0 and 3, regardless of titer

POSTEXPOSURE PROPHYLAXIS

POSTEXPOSURE PROPHYLAXIS

• Wash lesions well with soap and water (tetanus booster ad hoc)

• Infiltrate rabies immune globulin (20 IU/kg) into and around the margin of the bites

• Administer vaccine on days 0,3,7,14, and 28

Control of RabiesControl of Rabies

• Urban - canine rabies accounts for more than 99% of all human rabies. Control measures against canine rabies include;

– stray dog control.

– Vaccination of dogs

– quarantine of imported animals

• Wildlife - this is much more difficult to control than canine rabies. However, there are on-going trials in Europe where bait containing rabies vaccine is given to foxes. Success had been reported in Switzerland.

ArenavirusesArenaviruses

• Enveloped ssRNA viruses

• virions 80-150nm in diameter

• genome consists of 2 pieces of ambisense ssRNA.

• 7-8 nm spikes protrude from the envelope.

• host cell ribosomes are usually seen inside the outer membrane but play no part in replication.

• Members of arenaviruses include Lassa fever, Junin and Macupo viruses.

Lassa fever virus particles budding from the surface of an infected cell. (Source: CDC)

Lassa FeverLassa Fever

Found predominantly in West Africa, in particular Nigeria, Sierra Leone and Liberia.

The natural reservoir is multimammate rat (Mastomys)

Man may get infected through contact with infected urine and faeces.

Man to man transmission can occur through infected bodily fluids and Lassa fever had caused well-documented nosocomial outbreaks.

Mastomys

Clinical ManifestationsClinical Manifestations

• Incubation period of 3-5 days.

• Insidious onset of non-specific symptoms such as fever, malaise, myalgia and a sore throat.

• Typical patchy or ulcerative pharyngeal lesions may be seen.

• Severe cases may develop the following:– Myocarditis

– Pneumonia

– Encephalopathy

– Haemorrhagic manifestations

– Shock

• The reported mortality rate for hospitalized cases of Lassa fever is 25%. It carries a higher mortality in pregnant women.

Laboratory DiagnosisLaboratory Diagnosis

Lassa fever virus is a Group 4 Pathogen. Laboratory diagnosis should only be carried out in specialized centers.

– Detection of Virus Antigen - the presence of viral antigen in sera can be detected by EIA. The presence of viral antigen precedes that of IgM.

– Serology - IgM is detected by EIA. Using a combination of antigen and IgM antibody tests, it was shown that virtually all Lassa virus infections can be diagnosed early.

– Virus Isolation - virus may be cultured from blood, urine and throat washings. Rarely carried out because of safety concerns.

– RT-PCR - being used experimentally.

Management and Prevention

Management and Prevention

• Good supportive care is essential.• Ribavirin - had been shown to be effective against Lassa fever with a 2

to 3 fold decrease in mortality in high risk Lassa fever patients. Must be given early in the illness.

• Hyperimmune serum - the effects of hyperimmune serum is still uncertain although dramatic results have been reported in anecdotal case reports.

• Postexposure Prophylaxis - There is no established safe prophylaxis. Various combinations of hyperimmune immunoglobulin and/or oral ribavirin may be used.

• There is no vaccine available, prevention of the disease depends on rodent control.

HantavirusesHantaviruses

• Forms a separate genus in the Bunyavirus family.

• Unlike under bunyaviridae, its transmission does not involve an arthropod vector.

• Enveloped ssRNA virus.

• Virions 98nm in diameter with a characteristic square grid-like structure.

• Genome consists of three RNA segments: L, M, and S.

HistoryHistory

• Haemorrhagic Fever with Renal Syndrome (HFRS: later renamed hantavirus disease) first came to the attention of the West during the Korean war when over 3000 UN troops were afflicted.

• It transpired that the disease was not new and had been described by the Chinese 1000 years earlier.

• In 1974, the causative was isolated from the Korean Stripped field mice and was called Hantaan virus.

• In 1995, a new disease entity called hantavirus pulmonary syndrome was described in the “four corners” region of the U.S.

Some Subtypes of hantaviruses associated with human diseaseSome Subtypes of hantaviruses associated with human disease

• Hantaan, Porrogia and related viruses - This group is found in China, Eastern USSR, and some parts of S. Europe. It is responsible for the severe classical type of hantavirus disease. It is carried by stripped field mice. (Apodemus agrarius)

• Seoul type - associated with moderate hantavirus disease. It is carried by rats and have a worldwide distribution. It has been identified in China, Japan, Western USSR, USA and S.America.

• Puumala type - mainly found in Scandinavian countries, France, UK and the Western USSR. It is carried by bank voles (Clethrionomys glareolus) and causes mild hantavirus disease (nephropathia epidemica).

• Sin Nombre - found in many parts of the US, Canada and Mexico. Carried by the Deer Mouse (Peromyscus maniculatus) and causes hantavirus pulmonary syndrome.

Rodent Carriers of Hantaviruses

Rodent Carriers of Hantaviruses

Stripped field mouse (Apodemus agrarius)

Bank vole (Clethrionomys glareolus)

Deer Mouse (Peromyscus maniculatus) Rat (Rattus)

Clinical Features of Hantavirus Disease

Clinical Features of Hantavirus Disease

• The multisystem pathology of HVD is characterized by damage to capillaries and small vessel walls, resulting in vasodilation and congestion with hemorrhages.

• Classically, hantavirus disease consists of 5 distinct phases. These phases may be blurred in moderate or mild cases.

– Febrile phase - abrupt onset of a severe flu-like illness with a erythematous rash after an incubation period of 2-3 days.

– Hypotensive phase - begins at day 5 of illness

– Oliguric phase - begins at day 9 of illness. The patient may develop acute renal failure and shock. Haemorrhages are usually confined to petechiae. The majority of deaths occur during the hypotensive and oliguric phases

– Diuretic phase - this occurs between days 12-14 .

– Convalescent phase - this may require up to 4 months.

Nephropathia Far Eastern Rat-bourne Balkan Epidermica HVD HVD HVD Virus type Puumala Hantaan Seoul Porogia Overall Severity 1-2 2-4 1-3 2-4 Multiphasic Disease occasionally Yes Blurred Yes Renal Abnormalities 1-2 4 1-2 4 Hepatic abnormalities 0 0-1 1-3 0-1 Haemorrhagic phenomenon 0-1 1-4 1-2 1-4 Mortality <1% 5-10% 1% 5-35% Score = 0 to 4

Comparative Clinical Features of Recognized Hantavirus Disease (HVD)

Hantavirus Pulmonary Syndrome (HPS)

Hantavirus Pulmonary Syndrome (HPS)

• More than 250 cases of HPS have been reported throughout North and South America with a mortality rate of 50%

• In common with classical HVD, HPS has a similar febrile phase.

• However, the damage to the capillaries occur predominantly in the lungs rather than the kidney.

• Shock and cardiac complications may lead to death.

• The majority of HPS cases are caused by the Sin Nombre virus. The other cases are associated with a variety of other hantaviruses e.g. New York and Black Creek Canal viruses.

DiagnosisDiagnosis

• Serological diagnosis - a variety of tests including IF, HAI, SRH, ELISAs have been developed for the diagnosis of HVD and HPS.

• Direct detection of antigen - this appears to be more sensitive than serology tests in the early diagnosis of the disease. The virus antigen can be demonstrated in the blood or urine.

• RT-PCR - found to of great use in diagnosing hantavirus pulmonary syndrome.

• Virus isolation - isolation of the virus from urine is successful early in hantavirus disease. Isolation of the virus from the blood is less consistent. Sin Nombre virus has never been isolated from patients with HPS.

• Immunohistochemistry - useful in diagnosing HPS.

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National Statutory Notifiable Communicable Diseases

• Group A: Plague, Cholera

• Group B: SARS, AIDS, Viral hepatitis, Poliomyelitis, HPAI,

Measles, HFRS, Rabies, Japanese encephalitis, Dengue fever, Anthrax, Bacillary & amebic dysentery, TB, Typhoid fever/Paratyphoid fever, Meningococcal Meningitis, Pertussis, Diphtheria, Neonatal Tetanus, Scarlet fever, Brucellosis, Gonorrhea, Syphilis, Leptospirosis, Schistosomiasis, Malaria

• Group C: Influenza, Mumps, Rubella, Acute hemorrhagic Conjunctivitis, Leprosy, Epidemic typhus/Endemic typhus, kala-azar, Echinococcosis, Filariasis, Infectious diarrhea

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Animal Health - Human Health Collaboration -Animal Health - Human Health Collaboration -

• “Effective control of zoonotic disease relies on active involvement of both veterinary and human health services.”

• “This dual involvement needs to take place at every stage, from research, organizing funding, planning, surveillance, creating public awareness, to implementing the actual control activities.”

TULAREMIATULAREMIA

Dunne - CIDP January 18, 2005

TularemiTularemi

• Francisella tularensis is the causative agent of tularemia (a reportable disease)

• F. tularensis is a small, Gram-negative, nonmotile, encapsulated, pleomorphic coccobacillus (short rod).

• It is a facultative intracellular parasite that grows poorly or not at all on most lab media and requires a special blood agar

Dunne - CIDP January 18, 2005

• Human commonly acquires tularemia via• the insect bites (ticks primarily, but also

deer flies, mites, blackflies, or mosquitoes) or

• by handling infected animal tissues. Human disease (rabbit or deer fly fever) is characterized by a focal ulcer at the site of entry of the organisms and enlargement of the regional lymph nodes.

Dunne - CIDP January 18, 2005

• As few as10-50 bacilli will cause disease in humans if inhaled or introduced intradermally, whereas a very large inoculum (~108 organisms) is required for the oral route of infection.

Dunne - CIDP January 18, 2005

• Incubation period is 3-10 days.

• A small skin papule usually develops at the site of entry.

• Ulceration occurs together with fever, chills, malaise, fatigue, and usually lymphadenopathy.

Dunne - CIDP January 18, 2005

• Bacteremia usually occurs and the bacilli then grow intracellularly in the reticuloendothelial system.

• Dissemination of the organisms through the bloodstream permits focal lesions to develop in numerous organs

Dunne - CIDP January 18, 2005

EpidemiologyEpidemiology

• Summer peak related to ticks– 90% pediatric cases

• Winter peak related to trapping and hunting of rabbits

Photo courtesy of National Archives

TularemiaTularemia

Geographic distributionGeographic distribution

Clinical ManifestationsClinical Manifestations

• Six classic froms;– Ulceroglandular– Glandular– Oculoglandular– Pharyngeal– Typhoidal– Pneumonie

Diagnosis of tularemiaDiagnosis of tularemia

• Clinical suspicion• Organism rarely seen on Gram stained

smears• Direct fluorescent antibody staining of

smears,tissues• Antigen detection in urine• PCR• Most common way of diagnosis serology

(tube agg, microagg, hemagg, ELISA)

TreatmentTreatment• First choice is streptomycin

• Gentamycin alternative

YERSINIAYERSINIA

Dunne - CIDP January 18, 2005

Yersinia pestisYersinia pestis• Plague, disease of antiquity

• Three catastrophic pandemics

• Latest pandemic began in China in the 1860s.

• Recently resurged in sub-Saharan Africa.

• Aerosol weapon during the Cold War (catagory A biologic agent).

Yersinia pestisYersinia pestis• Gram negative, bipolar-staining bacillus

• Grows aerobically on most culture media, more slowly and optimally at 28°C

• Non-motile and non-spore forming

• Not ferment lactose

• Citrate, urease and indole negative

Transmission of plagueTransmission of plague

• Plague is primarily an infection of animals

• Transmitted by flea bites

• Domestic rats are the most dangerous reservoirs

• Most efficient vector to humans is oriental rat flea

Clinical manifestationsClinical manifestations

• Bubonic

• Septicemic

• Pneumonic

• Pharingeal

• Meningitis

• Fever, painful lymphadenopathy (bubo)

• Fever, hypotension comp. of inflammatory response syndrome

• Cough, hemoptysis with /without bubo

• Painful, inflamed pharinx, local lymphadenopathy

• Fever, nuchal rigidity with bubo

DiagnosisDiagnosis• WBC elevated (10.000-20.000)

predominance of neutrophils

• Clinical specimens (blood, bubo aspirate)

• Chest x-rays

• Serologic test (passive hemagg test, ELISA,), PCR

TreatmentTreatment• Streptomycin drug of choice

• Gentamicin

• Tetracycline

• Chloramphenicol

BRUCELLOSISBRUCELLOSIS

Dunne - CIDP January 18, 2005

• Brucella are Gram-negative, nonmotile, coccobacilli. They are strict aerobes that grow very slowly (fastidious) on blood agar. In the host, they live as facultative intracellular pathogens.

Dunne - CIDP January 18, 2005

• Brucellosis is primarily a disease of animals and it affects organs rich in the sugar erythritol (breast, uterus, epididymis, etc.). The organism localizes in these animal organs and causes infertility, sterility, mastitis, abortion, or resides as carriage. Humans in close contact with infected animals (slaughterhouse workers, veterinarians, farmers, dairy workers) are at risk of developing undulant fever.

Dunne - CIDP January 18, 2005

PATHOGENSPATHOGENS

• Four different species of Brucella are known to infect humans:

• B. abortus (cattle),

• B. suis (swine),

• B. melitensis (goats/sheep) and

• B. canis (dogs).

Dunne - CIDP January 18, 2005

• B. abortus and B. canis cause a mild suppurative febrile infection whereas B. suis causes a more severe suppurative infection which can lead to destruction of the lymphoreticular organs and kidney.

• B. melitensis is the cause of most severe and prolonged recurring disease.

Dunne - CIDP January 18, 2005

PATHOGENESISPATHOGENESIS

• The bacteria enter the human host through the mucous membranes of the oropharynx (ingestion/inhalation routes), through abraded skin, or through the conjunctiva.

• Usually infection occurs by direct contact with infected material, although it may also occur by ingestion of milk or milk products.

Dunne - CIDP January 18, 2005

TREATMENTTREATMENT

• Prolonged treatment with Tetracyclin combined with Rifampin that penetrates cells, is effective.

• Control measures include animal vaccination and avoidance of infected material (e.g., unpasteurized dairy products).

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• The symptoms in brucellosis are due to the presence of the organism and appear 2-4 weeks (sometimes up to 2 months) after exposure.

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• Diagnosis is based on prolonged (at least a week) presence of undulant fever, myalgia, arthralgia and the history of exposure (contact with animals or consumption of unprocessed material from infected animals). Definitive diagnosis can be made by culturing blood samples on blood-enriched media. The (fastidious) organisms grow very slowly (4-6 weeks in blood culture). B. abortus but not other Brucella grow better in 5% CO2 atmosphere (microaerophilic). On blood agar, they produce white glistening colonies.

• Specific antibodies can be used to further confirm the diagnosis

Dunne - CIDP January 18, 2005

QUESTION