Diseases / List of Fungal / Algal Diseases / Disease description:

Cryptococcosis in Ferrets 

INFORMATION AVAILABLE

GENERAL INFORMATION

CLINICAL CHARACTERISTICS & PATHOLOGY

INVESTIGATION & DIAGNOSIS

TREATMENT & CONTROL

SUSCEPTIBILITY & TRANSMISSION

ENVIRONMENT & GEOGRAPHY

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General and References

Disease Summary

Fungal disease acquired by inhalation of spores; disseminated disease is usually seen only in immunosuppressed individuals.
Ferret A fungal disease causing a wide spectrum of clinical signs in ferrets: chronic weight loss, respiratory signs typical of chronic rhinitis, signs of lower respiratory tract disease, CNS signs, cutaneous lesions, localised masses of the nose or a distal extremity, intra-abdominal masses or lymphadenopathy.

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Alternative Names (Synonyms)

  • Cryptococus neoformans infection
  • Cryptococcus gatti infection
  • Torulosis

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Disease Type

Fungal Infection

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Infectious/Non-Infectious Agent associated with the Disease

  • Cryptococus neoformans (including Cryptococus neoformans var neoformans and Cryptococus neoformans var grubii)
  • Cryptococcus gatti (Cryptococcus bacillisporus, Cryptococus neoformans var gattii)

A round yeast, 3.5 - 7 um diameter, with a thick heteropolysacharide capsule, 1 Ám - 30 Ám thick. (J213.6.w3)

Infective "Taxa"

  • --

Non-infective agents

--

Physical agents

-- Indirect / Secondary

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References

Disease Author

Dr Debra Bourne MA VetMB PhD MRCVS (V.w5)
Click image for main Reference Section

Major References / Reviews

Code and Title List

General: J84.15.w3

Ferrets:
J4
.225.w7, J4.236.w1, J14.43.w4, J24.78.w2, J213.6.w3

Other References

Code and Title List

J4.184w3, J24.58.w2, J42.64.w1

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Clinical Characteristics and Pathology

Detailed Clinical and Pathological Characteristics

General  

Clinical Characteristics

Variable.
  • Often upper respiratory signs, pneumonia, subcutaneous nodules, lymphadenopathy, CNS signs or ocular signs. (J84.15.w3)
  • Respiratory signs are common in most studies. (J4.225.w7)
  • In a series of 39 cases from British Columbia, Canada, in 2003, often non-specific CNS signs (seizures, ataxia, generalised weakness, blindness, nystagmus), upper respiratory tract signs (nasal discharge, other signs), skin nodules and abdominal masses. CNS signs may be seen alone or with e.g. nasal discharge. (J4.225.w7)
Ferret A wide spectrum of clinical signs may occur in ferrets: chronic weight loss, respiratory signs typical of chronic rhinitis, signs of lower respiratory tract disease, CNS signs, cutaneous lesions, localised masses of the nose or a distal extremity, intra-abdominal masses or lymphadenopathy.
  • In a three-year-old male ferret used for rodent control around an aviary to which many wild pigeons were attracted. Lethargy and possibly some respiratory signs, then sudden death. (J24.58.w2)
  • In a three-year-old male ferret, posterior paralysis (considered to be associated with vertebral disc disease) and listlessness. Other clinical signs were associated with congestive cardiomyopathy. (J4.184.w3)
  • A mature male ferret was found dead. (J42.64.w1)
  • In a five-year-old castrated male ferret, a subcutaneous swelling on the bridge of the nose, present for several months, with more recent onset lethargy, coughing and sneezing. (J24.78.w2)
  • In a four-year-old castrated male ferret, weight loss over a period of 1.5 months, recent lethargy progressing to retching and diarrhoea over two days. On physical examination, quiet, in poor body condition, with increased respiratory effort and retching. Spleen palpably enlarged. On radiography, a pulmonary bronchointerstitial pattern was revealed. Ultrasound of the abdomen indicated multiple enlarged mesenteric lymph nodes, plus a possible pancreatic mass. Exploratory laparotomy revealed an enlarged, greenish-yellow portal lymph node, which was excised. (J4.236.w1)
  • In two ferrets on Vancouver Island, British Columbia, Canada, in 2000-2001, one had a subcutaneous mass and one had lymphadenopathy. (J14.43.w4)
  • In two ferrets in British Columbia, Canada, in 2003: (J4.225.w7)
    • respiratory signs including nasal discharge in one ferret; (J4.225.w7)
    • signs of acute abdominal discomfort plus a palpable abdominal mass in the second ferret. (J4.225.w7)
  • In a six-year old ferret, sibling of the ferret with nasal cryptococcosis, lethargy, hair loss and weight loss developed a year later, with superficial cervical and popliteal lymphadenopathy; a mass developed caudal to the angle of the jaw on the right side and purulent material from this contained yeasts; Cryptococcus bacillisporus (Cryptococcus neoformans var gatti) was grown. (J24.80.w3)
  • In a two-year-old castrated male ferret from Sydney, dyspnoea, lethargy and weakness, poor body condition and death following anaesthesia for investigation. (J24.80.w3)
  • In a 2-3-year-old spayed female ferret from Sydney, the history was of a few days of lethargy, inappetance and gagging; an abdominal mass had been palpated a couple of months earlier. On physical examination poor body condition, "panting" respiration, slight cyanosis and a sausage-shaped abdominal mass were found. The ferret died during anaesthesia for investigation. Radiographs confirmed the abdominal mass and showed diffuse alveolar disease. (J24.80.w3)
  • In a 3.5-year-old castrated male ferret from Sydney, lethargy, poor appetite and a grossly swollen distal left forelimb (twice normal size), which became ulcerated. (J24.80.w3)
  • In a 1.75-year-old castrated male ferret from Vancouver Island, Canada, abrupt development of a firm, hairless and ulcerated mass, 1.2 cm diameter, on the second digit of the left hind leg. (J24.80.w3)
  • In a three-year-old male ferret from Vancouver, hind limb weakness, swelling of the distal part of the left hind leg, and enlargement of the popliteal lymph node on that side, together with inappetance; the ferret was noted to be thin. (J24.80.w3)

Incubation

One case in a dog developed three months after a journey to the epicentre of an outbreak, while a cat developed disease mine months after moving away from the area. (J14.43.w4)
Ferret
  • --

Mortality / Morbidity

  • In one study of 38 animals, 19 (half) of the affected animals (mainly dogs and cats, plus two ferrets and one cockatoo) survived with treatment including various antifungal drugs plus, where appropriate , surgical resection of cutaneous granulomas. (J4.225.w7)
Ferret
  • Several cases have been diagnosed only at necropsy. (J24.78.w2)

Pathology

--
Ferret
Gross Pathology
  • In a mature male ferret: (J42.64.w1)
    • Abdomen: Serosal surfaces of organs covered with a thick layer of colourless gelatinous material, easily peeled from the serosa. Extensive fibrous adhesions between organs.
    • GIT: On the serosal surface of the intestines, a few 1 mm diameter firm white nodules.
    • Mesenteric lymph nodes: moderately enlarged; on the cut surfaces, a few 1 mm diameter firm white nodules.
    • Spleen, liver: scattered 1 mm diameter firm white nodules.

    (J42.64.w1)

  • In a four-year-old castrated male ferret: (J4.236.w1)
    • Pulmonary: lungs brown-tan, diffusely firm.
    • Hepatic: liver slightly pale.
    • Renal: In the right kidney, a 3 x 2 x 0.5 cm cyst in the cortex.
    • Pancreas: 3 mm firm, yellow-tan nodule.
    • Splenic: enlarged spleen.
    • Lymph nodes: cervical, mandibular, retropharyngeal, axillary, gastric, pancreatic, tracheobronchial and mesenteric lymph nodes enlarged.
Histopathology
  • In a three-year-old male ferret used for rodent control around an aviary to which many wild pigeons were attracted. (J24.58.w2)
    • Pulmonary: In lung sections, thick-walled budding yeast present. (J24.58.w2)
  • In a three-year-old male ferret, posterior paralysis and listlessness. Other clinical signs were associated with congestive cardiomyopathy. (J4.184.w3)
    • CNS: Cerebral and cerebellar diffuse, marked meningeal infiltrate of lymphocytes, with moderate quantities of round, pale budding organisms, 5-15 um diameter; these were identified as Cryptococcus neoformans. (J4.184.w3)
  • In a mature male ferret: (J42.64.w1)
    • Gelatinous material: masses of yeast-ike organisms, each about 10 um diameter and surrounded by a mucoid capsule about 1 um thick. The capsule was positive with periodic-acid-Schiff, showed metachromatic staining with toludene blue, and had a strong affinity for mucicarmine. A few leucocytes were present, mainly neutrophils.
    • Nodules: small tubercule-like granulomata of macrophages andmultinucleated giant cells, with small numbers of similar yeast-like organism in the cytoplasm of these cells. The morphology and staining were considered typical of cryptococci.
  • In a four-year-old castrated male ferret: (J4.236.w1)
    • Lungs, spleen, lymph nodes: numerous spherical 12 - 25 um pale basophilic yeast-like organisms with a central nucleus and thick capsule. Narrow-based budding was visible on a few organisms. The organisms were consistent with Cryptococcus neoformans. Granulomatous to pyogranulomatous inflammatory infiltrates of epithelioid macrophages, lymphocytes and neutrophils surrounded the yeasts.
    • CNS: in the cerebellum, pons and frontal lobe, similar organisms but no inflammatory response.
    • Liver: mild fatty change.
    • Spleen: extramedullary haematopoisis.
    • Pancreas: (pancreatic nodule on gross necropsy): acinar-cell adenomatous hyperplasia.
    • Kidney: (cyst on gross necropsy): cystically dilated renal tubules and glomeruli.

    (J4.236.w1)

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Human Health Considerations

Humans can also be infected from the same sources that infect animals. 

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Susceptibility / Transmission

General information on Susceptibility / Transmission

Transmission
  • This organism is acquired from the environment. Cryptococcus neoformans is associated particularly with bird droppings with Cryptococcus gattii is associated with Eucalyptus trees and, more recently, a variety of other trees as well as soil, fresh water and sea water in the Pacific Northwest of North America. (J84.15.w3, J14.43.w4, J213.6.w3)
  • Disturbance of soil by digging, hiking, logging and construction activities, which may increase aerial dispersal of infectious particles, are recognised risk factors for animals. (J84.15.w3)
Susceptibility
  • Disease may occur in healthy, immunocompetent individuals as well as in immunocompromised individuals. (J84.15.w3)
  • Disease may either be primary, or involve reactivation of a latent, subclinical infection. (J84.15.w3)
Ferret
Transmission
  • Note: while some cases have been seen in, for example, ferrets which enjoy digging outside (J24.80.w3), at least one case in a ferret was seen in an indoor-housed ferret with no known access to soil. (J4.236.w1)
Susceptibility
  • In a three-year-old male ferret, treatment with dexamethasone for suspected intravertebral disk disease might have contributed to invasion, although the intense lymphocytic reaction present in the meninges at the time of death suggests the ferret was not immunosuppressed at that time. (J4.184.w3)

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Disease has been reported in either the wild or in captivity in:

  • In a three-year-old male ferret used for rodent control around an aviary to which many wild pigeons were attracted. (J24.58.w2)
  • In a four-year-old castrated male ferret in the USA; the ferret lived indoors. (J4.236.w1)
  • In two ferrets on Vancouver Island, British Columbia, Canada, in 2000-2001, as part of a multi-species outbreak also involving humans, cats, dogs, llamas and cetaceans (Dall's porpoises and Harbour porpoises). (J14.43.w4)
  • Note: as well as humans, dogs, cats, ferrets, porpoises, llamas, alpacas, a horse and birds have been confirmed with cryptococcosis in British Columbia (Canada), Washington state and Oregon (USA). (J84.15.w3)

Further information on Host species has only been incorporated for species groups for which a full Wildpro "Health and Management" module has been completed (i.e. for which a comprehensive literature review has been undertaken). Host species with further information available are listed below:

Host Species List

(List does not contain all other species groups affected by this disease)

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Disease has been specifically reported in Free-ranging populations of:

  • In cetaceans (Dall's porpoises and Harbour porpoises) around Vancouver Island, British Columbia, Canada, in 2000-2001, as part of a multi-species outbreak. (J14.43.w4)

Further information on Host species has only been incorporated for species groups for which a full Wildpro "Health and Management" module has been completed (i.e. for which a comprehensive literature review has been undertaken). Host species with further information available are listed below:

Host Species List

  • --

(List does not contain all other species groups affected by this disease)

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Environment/Geography

General Information on Environmental Factors/Events and Seasonality

  • In Australia, Cryptococcus gatti (Cryptococcus neoformans var gatti) has traditionally been associated with Eucalyptus trees. A study on Vancouver Island following an outbreak of cases in humans and domestic and wild animals, 2000-2001 isolated this organism from trees and soil around the central east coast of the island, including fir, alder, Garry oak, maple, cedar and pine and from air samples around tree stands. (J14.43.w4)

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Regions / Countries where the Infectious Agent or Disease has been recorded

  • Australia. (J24.78.w2)
  • USA. (J4.236.w1)
  • Vancouver Island and mainland British Columbia, Canada. (J14.43.w4)
  • Washington state and Oregon (USA). (J84.15.w3)

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Regions / Countries where the Infectious Agent or Disease has been recorded in Free-ranging populations

  • Around Vancouver Island, British Columbia, Canada. (J14.43.w4)

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General Investigation / Diagnosis

General Information on Investigation / Diagnosis

  • Consider cryptococcosis in individuals with upper respiratory signs, pneumonia, subcutaneous nodules, lymphadenopathy, unusual neurological signs, ocular signs or non-specific malaise (J4.225.w7, J84.15.w3)
  • Respiratory signs are common in most studies. (J4.225.w7)
  • In a series of 39 cases from British Columbia, Canada, in 2003, often non-specific CNS signs (seizures, ataxia, generalised weakness, blindness, nystagmus), upper respiratory tract signs (nasal discharge, other signs), skin nodules and abdominal masses. CNS signs may be seen alone or with e.g. nasal discharge. (J4.225.w7)
  • Cytological examination of specimens such as material from nasal flushes or nasal exudates, CSF, aspirates or impression smears from skin/subcutaneous masses, biopsy specimens from affected tissues, or histological specimens obtained at necropsy, usually clearly reveal the organisms: central yeast structures 3 - 12 um diameter, with narrow-based budding and clear surrounding halos. (J4.225.w7)
  • Antigen tests are highly sensitive and highly specific. In one series, 20/22 animals were positive; one dog with CNS signs and one cat with respiratory signs receiving fluconazole treatment were negative. There was one false-positive at a dilution of 1:2. (J4.225.w7)
Ferret
  • Cryptococcosis should be considered as a diagnosis in ferrets with chronic rhinitis ("snuffles"), pneumonia or pleurisy, cutaneous/subcutaneous or intra-abdominal masses, CNS disease or enlarged lymph node(s). (J24.80.w3)
  • Presumptive diagnosis can be made by detection of the organism in aspirated material from masses or lymph nodes, impression smears of ulcerated lesions, nasal discharge, CSF or fluid from bronchiolar lavage, as well as by histopathological examination of excised masses. If cryptococcosis is suspected, the LCAT (latex cryptococcal antigen test) can be carried out on serum; this has high sensitivity and specificity, although it may be negative early in infection. Several cases have been diagnosed only by histopathological examination of tissues following necropsy. Culture or immunohistochemistry can be used to confirm the identity of the organism. PCR fingerprinting can be carried out for further identification of the species/strain of Cryptococcus involved. (J213.6.w3, J24.80.w3)
  • Note: although suspicion of the disease is higher in regions where the organism is known to be a problem, and in ferrets with access to the outdoors, it should be remembered that this disease has been seen in an indoor-kept ferret in a region not known for this disease. (J4.225.w7, J4.236.w1)

Examples:

  • In a five-year-old castrated male ferret, histopathological examination of the excised subcutaneous swelling on the bridge of the nose revealed characteristic Cryptococcus organisms. A fine needle aspirate form the nasal swelling, stained with Diff-Quik, showed numerous spherical capsulated yeasts as well as large numbers of macrophages and smaller numbers of neutrophils and lymphocytes. Baseline LCAT titre was 1024. On culture, Cryptococcus neoformans grew on Sabourard's dextrose agar and was identified as Cryptococcus neoformans var. gatti. (J24.78.w2)
  • In a four-year-old castrated male ferret, diagnosis made on the basis of histopathological examination of a lymph node excised at exploratory laparotomy: multifocal clusters of 10 - 15 um encapsulated yeast-like organisms, staining pale blue, within the parenchyma. Diffuse hyperplasia of the lymphoid tissue, with the follicular architecture showing regional destruction and the medulla filled with macrophages and lymphocytes. PCR of extracted lung tissue to amplify the ITS (internal transcribed spacer) of the ribosomal RNA gene followed by sequencing confirmed the presence of Cryptococcus neoformans var grubii. (J4.236.w1)
  • In a six-year old ferret, sibling of the ferret with nasal cryptococcosis, examination of purulent material from the mass on the jaw showed that this contained yeasts; Cryptococcus bacillisporus (Cryptococcus neoformans var gatti) was grown from this material . (J24.80.w3)
  • In a two-year-old castrated male ferret from Sydney, diagnosis was made following necropsy, with the organism demonstrated on histological examination of the lungs and mediastinal lymph nodes. Immunohistochemistry confirmed Cryptococcus bacillisporus (Cryptococcus neoformans var gatti). (J24.80.w3)
  • In a 2-3-year-old spayed female ferret from Sydney with an abdominal mass, the organism was demonstrated on histological examination of the abdominal (intestinal) mass, mesenteric lymph nodes and (in small numbers) lung and liver. Immunohistochemistry identified the organism as Cryptococcus neoformans var grubii (formerly known as Cryptococcus neoformans var neoformans serotype A). (J24.80.w3)
  • In a 3.5-year-old castrated male ferret from Sydney with a swollen forelimb, organisms morphologically consistent with Cryptococcus were demonstrated in a DiffQuick stained impression smear from the ulcerated leg lesion. Cryptococcal antigen was present in serum at a titre of greater than 2048. (J24.80.w3)
  • In a 1.75-year-old castrated male ferret from Vancouver Island, Canada, the organism was found on histological examination of the surgically-excised affected digit. Immunohistochemistry indicated Cryptococcus neoformans var grubii. (J24.80.w3)
  • In a three-year-old male ferret from Vancouver, the organism was detected on examination of a biopsy specimen from the popliteal lymph node and confirmed with immunohistochemistry as Cryptococcus neoformans var grubii. (J24.80.w3)
Related Techniques
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Similar Diseases (Differential Diagnosis)

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Ferret
  • Other causes of chronic rhinitis ("snuffles"), pneumonia or pleurisy, cutaneous/subcutaneous or intra-abdominal masses, CNS disease or enlarged lymph node(s). (J24.80.w3)

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Treatment and Control

Specific Medical Treatment

  • In one series of 15 isolates from British Columbia, Canada, sensitivity was: (J4.225.w7)
Ferret Ferrets can be treated with antifungal medication such as Itraconazole or Fluconazole. These can be given as liquid paediatric formations, if available, or mixed with a small amount of Energel, Nutrigel or similar highly palatable flavoured energy supplements. Where possible, surgical debulking is recommended before starting antifungal medication. (J24.78.w2, J24.80.w3)
  • Fluconazole is considerably more expensive than itraconazole. The extra expense is justified in cases involving the eye, brain, meninges or urinary tract, since fluconazole reaches higher concentrations in these compartments when given at therapeutic doses, or if use of itraconazole leads to hepatotoxicity. (J24.78.w2)
  • Based on infection in cats and dogs, continuation of treatment until the LCAT titre reduces to zero is recommended to minimise the risk of recurrence. (J24.78.w2)

Examples:

  • A five-year-old castrated male ferret with invasive nasal cryptococcosis was treated with Itraconazole given orally. The initial dose was 25 mg/kg once daily, increased after three weeks to 33 mg/kg. This was well tolerated (appetite unchanged or increased, nasal cavity signs diminished and resolved, general status improved. After 171 days, there was no swelling of the nasal bridge, no signs of naval cavity disease, LCAT (latex cryptococcal antigen test) had declined to 128 and alanine aminotransferase was within the reference range, less than 60 U/L. The itraconazole dose was reduced to 25 mg once daily, to continue until LCAT declined to 16. (J24.78.w2)
    •  Itraconazole was given as 1/4 or 1/3 of a gel capsule of itraconazole mixed with a palatable nutritional supplement gel, Energel Veterinary Companies of Australia). (J24.78.w2)
    • Note: Treatment was continued for three years with the LCAT remaining at 16-32, then stopped due to presumed systemic toxicity. The ferret was euthanased due to a cranial abdominal mass (hepatic carcinoma) three months later and at necropsy no cryptococcal organisms were present in the nasal cavity, CNS or other tissues. (J24.80.w3)
    • Note: surgical debulking is recommended prior to specific medical treatment if possible (see below). (J24.78.w2).
  • In a four-year-old castrated male ferret, treatment was initiated with Itraconazole10 mg/kg orally every 12 hours plus Amphotericin B 0.25 mg/kg (0.1 mg/lb) diluted in 5% dextrose and given intravenously once daily. (J4.236.w1)
    • The ferret deteriorated and died within a few days. (J4.236.w1)
  • A 3.5-year-old castrated male ferret from Sydney with, lethargy, poor appetite and a grossly swollen distal left forelimb was treated with Itraconazole, 25 mg/kg orally daily. Recovery was rapid, with the lesion no longer visible after five weeks. After six months, therapy was discontinued; the LCAT titre was less than 2 and (J24.80.w3)
  • A three-year-old male ferret from Vancouver, with infection of one hind limb was treated with Fluconazole, 12 mg orally every 12 hours. After four months of treatment it appeared well, with normal appetite, but was still dragging the affected leg. (J24.80.w3)
Related Techniques

 

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General Nursing and Surgical Techniques

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Ferret Surgical debulking of aggregations of fungal-infected tissues are recommended prior to medical treatment, if possible, since drugs may not penetrate the tissue if it contains mainly fungal elements. (J24.78.w2) Surgical excision alone has been apparently curative with a superficial, well-circumscribed lesion. (J24.80.w3)
  • In a five-year-old castrated male ferret with nasal cryptococcosis, the bulk of the nasal swelling was surgically excised for histopathological examination. (J24.78.w2)
  • In a 1.75-year-old castrated male ferret from Vancouver Island, Canada, with a lesion on one digit, excision of the affected digit (including all three phalanges) was apparently curative; there was no sign of recurrence of the infection four months later. The lesion had been well circumscribed and not involved bone. (J24.80.w3)
Related Techniques
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Preventative Measures

Vaccination --
Ferret --
Prophylactic Treatment

--

Ferret --
Related Techniques
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Environmental and Population Control Measures

General Environment Changes, Cleaning and Disinfection --

 

  • --
Population Control Measures --
  --
Isolation, Quarantine and Screening --
  --
Related Techniques
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