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==Overview==
Listeriosis can present in different ways depending on the type of infection, such as: [[fever]], [[headache]]and [[muscle ache]]s, sometimes preceded by [[diarrhea]] or other gastrointestinal symptoms. Other less common symptoms may include: [[stiff neck]], [[confusion]] and [[convulsions]]. Manifestations of listeriosis are host-dependent. In older adults and persons with immunocompromising conditions, [[septicemia]] and meningitis are the most common clinical presentations. Pregnant women may experience a mild, flu-like illness followed by fetal loss or [[bacteremia]] and [[meningitis]] in their newborns. Immunocompetent persons may experience acute febrile gastroenteritis or no symptoms.
 
 


==Symptoms==
==Symptoms==
*A person with listeriosis usually has [[fever]] and [[muscle ache]]s, sometimes preceded by [[diarrhea]] or other gastrointestinal symptoms. Almost everyone who is diagnosed with listeriosis has "invasive" infection, in which the bacteria spread beyond the gastrointestinal tract. The symptoms vary with the infected person:
===Febrile Gastroenteritis===
Febrile [[gastroenteritis]] accounts for less than 1% of reported bacterial food-born infections, occurring usually after ingestion of a large inoculum of bacteria from contaminated foods. Illness typically occurs 24 hours after ingestion of contaminated food and might present as:
*[[fever]]
*[[watery diarrhea]]
*[[nausea]]
*[[vomiting]]
*[[headache]]
*[[arthralgia|joint]] and [[myalgia|muscle pain]]
It generally lasts for 2 days and the patient experiences complete recovery from the symptoms. Some patients may be asymptomatic for the disease, while others, [[immunocompromised]], pregnant women and elder patients, in rare cases, present with invasive [[infection]]. ''L. monocytogenes'' [[infection]] should be considered when outbreaks of foodborne [[gastroenteritis]] surge and stool cultures fail to identify the [[pathogen]]<ref>{{Cite book  | last1 = Mandell | first1 = Gerald L. | last2 = Bennett | first2 = John E. (John Eugene) | last3 = Dolin | first3 = Raphael. | title = Mandell, Douglas, and Bennett's principles and practice of infectious disease | date = 2010 | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | isbn = 0-443-06839-9 | pages =  }}</ref>.
 
===Infection in Pregnancy===
[[Pregnant]] women suffer greater risk of ''L. monocytogenes'' [[infection]] because during [[pregnancy]] there is a slight impairment of [[cell-mediated immunity]]. ''Lysteria'' is also able to proliferate in the [[placenta]], in hard-to-reach areas for the [[immune system]]. Infection occurs more frequently during the third trimester of gestation, with an estimated 17 fold increase<ref>{{Cite book  | last1 = Mandell | first1 = Gerald L. | last2 = Bennett | first2 = John E. (John Eugene) | last3 = Dolin | first3 = Raphael. | title = Mandell, Douglas, and Bennett's principles and practice of infectious disease | date = 2010 | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | isbn = 0-443-06839-9 | pages =  }}</ref>, presenting most commonly with flu-like symptoms, such as:
*[[fever]]
*chills
*back pain
The infection may be mild and the diagnosis missed, if [[blood cultures]] are not obtained. Since [[bacteremia]], with no [[CNS]] involvement is common rule in pregnant women with [[listeriosis]], [[blood cultures]] should always be obtained in [[pregnant]] women who present with [[fever]], with no other alternative cause, such as [[UTI]] or [[pharyngitis]].
Because cell-to-cell transmission facilitates maternal-fetal transmission<ref>{{Cite book  | last1 = Mandell | first1 = Gerald L. | last2 = Bennett | first2 = John E. (John Eugene) | last3 = Dolin | first3 = Raphael. | title = Mandell, Douglas, and Bennett's principles and practice of infectious disease | date = 2010 | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | isbn = 0-443-06839-9 | pages =  }}</ref>, [[listeriosis]] in [[pregnant]] women, can result in:
*fetal death
*premature birth
*infected newborns
Among [[pregnant]] women with [[listeriosis]], 2/3 of the surviving infants develop clinical [[neonatal]] [[listeriosis]].<ref>{{Cite book  | last1 = Mandell | first1 = Gerald L. | last2 = Bennett | first2 = John E. (John Eugene) | last3 = Dolin | first3 = Raphael. | title = Mandell, Douglas, and Bennett's principles and practice of infectious disease | date = 2010 | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | isbn = 0-443-06839-9 | pages =  }}</ref>. The newborn also has great risk of developing [[granulomatosis]] infantiseptica, a severe ''[[in utero]]'' [[infection]] resulting from transplacental transmission, in which infants may present with:
*disseminated [[abscesses]]
*[[granulomas]] in multiple internal organs ([[brain]], [[lungs]], [[liver]], [[spleen]] and [[kidneys]])
*papular or ulcerative skin lesions.
*most infants with this disease are stillborn or die soon after birth.
 
''L. monocytogenes'' is one of the three major causes of [[neonatal]] [[meningitis]], worldwide. The early diagnosis and treatment of pregnant women infected with ''Listeria'' may lead to the birth of a normal healthy child.<ref>{{Cite book  | last1 = Mandell | first1 = Gerald L. | last2 = Bennett | first2 = John E. (John Eugene) | last3 = Dolin | first3 = Raphael. | title = Mandell, Douglas, and Bennett's principles and practice of infectious disease | date = 2010 | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | isbn = 0-443-06839-9 | pages =  }}</ref>
 
===Sepsis of Unknown Origin===
Occurs in patients of all ages. [[Neonates]] usually tend to acquire the infection during or after [[birth]]. When this occurs during the first week of life, it usually manifests as [[sepsis]], while after this first week, it tends to have more variable manifestations, such as [[meningitis]].
Early onset of [[sepsis]] is associated with higher [[neonatal]] mortality. In this case, ''L. monocitogenes'' can be isolated from [[conjunctivae]], [[amniotic fluid]], [[meconium]], [[placental]] [[blood]], with higher concentrations of [[bacteria]] being found in the [[neonatal]] [[lung]] and [[gut]], which suggests that [[infection]] is acquired in [[utero]], by inhalation of [[infected]] [[amniotic fluid]].<ref>{{Cite book  | last1 = Mandell | first1 = Gerald L. | last2 = Bennett | first2 = John E. (John Eugene) | last3 = Dolin | first3 = Raphael. | title = Mandell, Douglas, and Bennett's principles and practice of infectious disease | date = 2010 | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | isbn = 0-443-06839-9 | pages =  }}</ref>
 
*''Listerial [[meningoencephalitis]]'' is more common in neonates after 3 days of age, as well as in immunocompromised and elderly adults.
*Adults presenting ''Listerial [[sepsis]]'', are most commonly [[immunocompromised]] or elderly, and typically present with fever and chills. [[Septic shock]] can occur with [[brain]] and/or [[meningeal]] involvement, leading to [[meningoencephalitis]] or [[cerebritis]].
 
===Bacteremia===
After the [[neonatal]] period, the most common manifestation of [[listeriosis]] is [[bacteremia]] without and evident focus of [[infection]]. The clinical manifestations include:
*[[Fever]]
 
*[[Myalgias]]
 
*[[Nausea]]
 
*[[Diarrhea]]
 
Since most of the times that healthy individuals experience these manifestations do not have their [[blood culture|blood cultured]], they have higher probability of transient [[bacteremias]] going undetected.<ref>{{Cite book  | last1 = Mandell | first1 = Gerald L. | last2 = Bennett | first2 = John E. (John Eugene) | last3 = Dolin | first3 = Raphael. | title = Mandell, Douglas, and Bennett's principles and practice of infectious disease | date = 2010 | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | isbn = 0-443-06839-9 | pages =  }}</ref>
 
===CNS Infection===
Because ''L. monocytogenes'' has tropism for the [[brain stem]] and [[meninges]], unlike other causes of [[bacterial meningitis]], ''Listeria'' tends to cause [[parenchymal]] [[brain]] [[infections]]. Therefore, most patients will experience altered consciousness, [[seizures]] and/or movement disorders, and will truly have [[meningoencephalitis]]. [[Central Nervous System]] [[infection]] most commonly manifests by [[meningoencephalitis]], while [[cerebritis]], which usually progresses into [[brain abscess]] and [[rhombencephalitis]], is a less common manifestation. "In a study from the Massachusetts General Hospital, with [[CNS]] [[listeriosis]] outside [[neonatal]] period and [[pregnancy]], the most common predisposing factor for developing ''listerial'' [[meningitis]] was [[malignancy]], the second most common factor being [[transplantation]], followed by [[alcoholism]] and [[liver disease]], [[immunosuppression]] and [[steroid]] treatment, [[diabetes mellitus]] and [[HIV]]".<ref>{{Cite book  | last1 = Mandell | first1 = Gerald L. | last2 = Bennett | first2 = John E. (John Eugene) | last3 = Dolin | first3 = Raphael. |title = Mandell, Douglas, and Bennett's principles and practice of infectious disease | date = 2010 | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | isbn = 0-443-06839-9 | pages =  }}</ref>.
 
'''1. Meningoencephalitis'''
Occurs more frequently in [[neonates]] after 3 days of age and in [[immunocompromised]] and elderly patients. The clinical presentation can range from mild [[fever]] and mental status changes, to a more aggressive course with [[coma]]. There may also be an [[encephalic]] component present, which will present with focal [[neurological]] signs, such as:
*[[Cranial nerve]] abnormalities
*[[Ataxia]]
*[[Tremors]]
*[[Hemiplegia]]
*[[Deafness]]
*[[Seizures]]
 
'''2. Cerebritis/ Encephalitis'''
Results from direct hematogenous invasion of [[cerebral]] [[parenchyma]], with or without [[meningeal]] involvement, probably representing an early localised [[infection]] of the [[parenchyma]], which might eventually progress into [[brain abscess]]. [[Cerebritis]] may occur alongside [[meningitis]] in the same patient.
In these cases, the clinical picture is dominated by ''altered consciousness'' or ''cognitive disfunction'', but may also manifest as<ref>{{Cite book  | last1 = Mandell | first1 = Gerald L. | last2 = Bennett | first2 = John E. (John Eugene) | last3 = Dolin | first3 = Raphael. |title = Mandell, Douglas, and Bennett's principles and practice of infectious disease | date = 2010 | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | isbn = 0-443-06839-9 | pages =  }}</ref>:
*[[Fever]]
*[[Headache]]
*[[Hemiplegia]]
 
'''3. Rhombencephalitis'''
Rare manifestation of CNS infection, which affects more commonly healthy individuals through the ingestion of ''Listeria'' contaminated food, often in outbreaks. Rhombencephalitis often follows a biphasic course, beginning with:
*[[Headache]]
*[[Fever]]
*[[Nausea]]
*[[Vomiting]]
 
Which lasts for about 4 days, and is followed by an abrupt onset of:
*Asymetrical [[cranial nerve]] [[palsies]]
*[[Ataxia]]
*[[Tremor]]
*Decreased [[consciousness]]
*[[Seizures]]
*[[Hemiparesis]] and/or hemisensory deficits
*[[Respiratory failure]]
 
Mortality is high and the survivors tend to experience serious sequelae.
 
'''4. Brain abscess'''
Most cases occur in patients at risk for [[infection]]. The [[subcortical]] [[abscesses]] tend to be located in the [[thalamus]], the [[pons]] and/or [[medulla]], sites which are rarely affected by other [[bacteria]].<ref>{{Cite book  | last1 = Mandell | first1 = Gerald L. | last2 = Bennett | first2 = John E. (John Eugene) | last3 = Dolin | first3 = Raphael. |title = Mandell, Douglas, and Bennett's principles and practice of infectious disease | date = 2010 | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | isbn = 0-443-06839-9 | pages =  }}</ref>.
 
'''5. Spinal cord infection'''
Rare cases of [[spinal cord]] involvement have been reported. However, if spinal symptoms develop, in the setting of [[acute bacterial meningitis]] of uncertain etiology, ''L. monocytogenes'' should be considered"<ref>{{Cite book  | last1 = Mandell | first1 = Gerald L. | last2 = Bennett | first2 = John E. (John Eugene) | last3 = Dolin | first3 = Raphael. |title = Mandell, Douglas, and Bennett's principles and practice of infectious disease | date = 2010 | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | isbn = 0-443-06839-9 | pages =  }}</ref>.
Despite the fact of ''Listeria'' being the most common [[infectious]] cause of rhombencephalitis, it must be distinguished from other [[infectious]] etiologies, such as:
*[[Herpes simplex]] [[encephalities]]
*[[Tuberculosis]]
*[[Toxoplasmosis]]
*[[Cryptococcosis]]
*[[Lyme disease]]
*[[Epstein-Barr virus]]
*[[Brucellosis]]
*[[JC virus]]
There are also noninfectious conditions which may cause [[brainstem]] and/or [[cerebral]] lesions, such as:
*[[Multiple sclerosis]]
*[[Sarcoidosis]]
*Systemic [[rheumatic diseases]]
*[[Lymphoma]]
*[[Paraneoplastic syndrome]]
 
The diagnosis of [[rhombencephalitis]] can be delayed by the fact that [[CSF]] analysis often reveals only mild abnormalities, but may be demonstrated by [[Magnetic resonance]].
 
===Endocarditis===
Listerial [[endocarditis]] affects the population at risk for ''[[streptococcus viridans]]'' [[endocarditis]], producing [[native valve endocarditis|native]] and [[prosthetic valve]] disease and having an elevated rate of septic complications. Listerial [[endocarditis]] alone, may be an indicator of a [[GI tract]] abnormality, such as [[cancer]]<ref>{{Cite book  | last1 = Mandell | first1 = Gerald L. | last2 = Bennett | first2 = John E. (John Eugene) | last3 = Dolin | first3 = Raphael. |title = Mandell, Douglas, and Bennett's principles and practice of infectious disease | date = 2010 | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | isbn = 0-443-06839-9 | pages =  }}</ref>.


:*Pregnant women: Pregnant women typically experience only a mild, flu-like illness. However, infections during pregnancy can lead to [[miscarriage]], [[stillbirth]], [[premature delivery]], or life-threatening infection of the newborn.
===Focal infections===
Most focal infections have no specific characteristics, but do share a most common host, the [[immunocompromised]] patient. These might include:
*[[Skin]] or [[eye]] [[infections]]


:*Persons other than pregnant women: Symptoms, in addition to fever and muscle aches, can include [[headache]], [[stiff neck]], [[confusion]], loss of balance, and [[convulsions]].
*Oculoglandular syndrome, [[pneumonia]], [[empyema]], [[myocarditis]], [[lymphadenitis]], [[septic arthritis]], [[osteomyelitis]] and [[necrotizing fasciitis]].


*Listeriosis can present in different ways depending on the type of infection. Manifestations of listeriosis are host-dependent. In older adults and persons with immunocompromising conditions, [[septicemia]] and meningitis are the most common clinical presentations. Pregnant women may experience a mild, flu-like illness followed by fetal loss or [[bacteremia]] and [[meningitis]] in their newborns. Immunocompetent persons may experience acute febrile gastroenteritis or no symptoms.
*[[Brain|Brain abscess]] and [[spinal]] [[abscesses]], as well as [[cholecystitis]], resulting from hematogenous dissemination.
*[[Acute hepatitis]], simulating [[viral hepatitis]], seen in patients with disseminated infections.
*[[Peritonitis]], seen in [[cirrhosis]] and continuous ambulatory [[peritoneal dialysis]] patients.


==References==
==References==

Revision as of 15:59, 22 July 2014

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Listeriosis can present in different ways depending on the type of infection, such as: fever, headacheand muscle aches, sometimes preceded by diarrhea or other gastrointestinal symptoms. Other less common symptoms may include: stiff neck, confusion and convulsions. Manifestations of listeriosis are host-dependent. In older adults and persons with immunocompromising conditions, septicemia and meningitis are the most common clinical presentations. Pregnant women may experience a mild, flu-like illness followed by fetal loss or bacteremia and meningitis in their newborns. Immunocompetent persons may experience acute febrile gastroenteritis or no symptoms.


Symptoms

Febrile Gastroenteritis

Febrile gastroenteritis accounts for less than 1% of reported bacterial food-born infections, occurring usually after ingestion of a large inoculum of bacteria from contaminated foods. Illness typically occurs 24 hours after ingestion of contaminated food and might present as:

It generally lasts for 2 days and the patient experiences complete recovery from the symptoms. Some patients may be asymptomatic for the disease, while others, immunocompromised, pregnant women and elder patients, in rare cases, present with invasive infection. L. monocytogenes infection should be considered when outbreaks of foodborne gastroenteritis surge and stool cultures fail to identify the pathogen[1].

Infection in Pregnancy

Pregnant women suffer greater risk of L. monocytogenes infection because during pregnancy there is a slight impairment of cell-mediated immunity. Lysteria is also able to proliferate in the placenta, in hard-to-reach areas for the immune system. Infection occurs more frequently during the third trimester of gestation, with an estimated 17 fold increase[2], presenting most commonly with flu-like symptoms, such as:

The infection may be mild and the diagnosis missed, if blood cultures are not obtained. Since bacteremia, with no CNS involvement is common rule in pregnant women with listeriosis, blood cultures should always be obtained in pregnant women who present with fever, with no other alternative cause, such as UTI or pharyngitis. Because cell-to-cell transmission facilitates maternal-fetal transmission[3], listeriosis in pregnant women, can result in:

  • fetal death
  • premature birth
  • infected newborns

Among pregnant women with listeriosis, 2/3 of the surviving infants develop clinical neonatal listeriosis.[4]. The newborn also has great risk of developing granulomatosis infantiseptica, a severe in utero infection resulting from transplacental transmission, in which infants may present with:

L. monocytogenes is one of the three major causes of neonatal meningitis, worldwide. The early diagnosis and treatment of pregnant women infected with Listeria may lead to the birth of a normal healthy child.[5]

Sepsis of Unknown Origin

Occurs in patients of all ages. Neonates usually tend to acquire the infection during or after birth. When this occurs during the first week of life, it usually manifests as sepsis, while after this first week, it tends to have more variable manifestations, such as meningitis. Early onset of sepsis is associated with higher neonatal mortality. In this case, L. monocitogenes can be isolated from conjunctivae, amniotic fluid, meconium, placental blood, with higher concentrations of bacteria being found in the neonatal lung and gut, which suggests that infection is acquired in utero, by inhalation of infected amniotic fluid.[6]

Bacteremia

After the neonatal period, the most common manifestation of listeriosis is bacteremia without and evident focus of infection. The clinical manifestations include:

Since most of the times that healthy individuals experience these manifestations do not have their blood cultured, they have higher probability of transient bacteremias going undetected.[7]

CNS Infection

Because L. monocytogenes has tropism for the brain stem and meninges, unlike other causes of bacterial meningitis, Listeria tends to cause parenchymal brain infections. Therefore, most patients will experience altered consciousness, seizures and/or movement disorders, and will truly have meningoencephalitis. Central Nervous System infection most commonly manifests by meningoencephalitis, while cerebritis, which usually progresses into brain abscess and rhombencephalitis, is a less common manifestation. "In a study from the Massachusetts General Hospital, with CNS listeriosis outside neonatal period and pregnancy, the most common predisposing factor for developing listerial meningitis was malignancy, the second most common factor being transplantation, followed by alcoholism and liver disease, immunosuppression and steroid treatment, diabetes mellitus and HIV".[8].

1. Meningoencephalitis Occurs more frequently in neonates after 3 days of age and in immunocompromised and elderly patients. The clinical presentation can range from mild fever and mental status changes, to a more aggressive course with coma. There may also be an encephalic component present, which will present with focal neurological signs, such as:

2. Cerebritis/ Encephalitis Results from direct hematogenous invasion of cerebral parenchyma, with or without meningeal involvement, probably representing an early localised infection of the parenchyma, which might eventually progress into brain abscess. Cerebritis may occur alongside meningitis in the same patient. In these cases, the clinical picture is dominated by altered consciousness or cognitive disfunction, but may also manifest as[9]:

3. Rhombencephalitis Rare manifestation of CNS infection, which affects more commonly healthy individuals through the ingestion of Listeria contaminated food, often in outbreaks. Rhombencephalitis often follows a biphasic course, beginning with:

Which lasts for about 4 days, and is followed by an abrupt onset of:

Mortality is high and the survivors tend to experience serious sequelae.

4. Brain abscess Most cases occur in patients at risk for infection. The subcortical abscesses tend to be located in the thalamus, the pons and/or medulla, sites which are rarely affected by other bacteria.[10].

5. Spinal cord infection Rare cases of spinal cord involvement have been reported. However, if spinal symptoms develop, in the setting of acute bacterial meningitis of uncertain etiology, L. monocytogenes should be considered"[11]. Despite the fact of Listeria being the most common infectious cause of rhombencephalitis, it must be distinguished from other infectious etiologies, such as:

There are also noninfectious conditions which may cause brainstem and/or cerebral lesions, such as:

The diagnosis of rhombencephalitis can be delayed by the fact that CSF analysis often reveals only mild abnormalities, but may be demonstrated by Magnetic resonance.

Endocarditis

Listerial endocarditis affects the population at risk for streptococcus viridans endocarditis, producing native and prosthetic valve disease and having an elevated rate of septic complications. Listerial endocarditis alone, may be an indicator of a GI tract abnormality, such as cancer[12].

Focal infections

Most focal infections have no specific characteristics, but do share a most common host, the immunocompromised patient. These might include:

References

  1. ↑ Mandell, Gerald L.; Bennett, John E. (John Eugene); Dolin, Raphael. (2010). Mandell, Douglas, and Bennett's principles and practice of infectious disease. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0-443-06839-9.
  2. ↑ Mandell, Gerald L.; Bennett, John E. (John Eugene); Dolin, Raphael. (2010). Mandell, Douglas, and Bennett's principles and practice of infectious disease. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0-443-06839-9.
  3. ↑ Mandell, Gerald L.; Bennett, John E. (John Eugene); Dolin, Raphael. (2010). Mandell, Douglas, and Bennett's principles and practice of infectious disease. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0-443-06839-9.
  4. ↑ Mandell, Gerald L.; Bennett, John E. (John Eugene); Dolin, Raphael. (2010). Mandell, Douglas, and Bennett's principles and practice of infectious disease. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0-443-06839-9.
  5. ↑ Mandell, Gerald L.; Bennett, John E. (John Eugene); Dolin, Raphael. (2010). Mandell, Douglas, and Bennett's principles and practice of infectious disease. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0-443-06839-9.
  6. ↑ Mandell, Gerald L.; Bennett, John E. (John Eugene); Dolin, Raphael. (2010). Mandell, Douglas, and Bennett's principles and practice of infectious disease. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0-443-06839-9.
  7. ↑ Mandell, Gerald L.; Bennett, John E. (John Eugene); Dolin, Raphael. (2010). Mandell, Douglas, and Bennett's principles and practice of infectious disease. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0-443-06839-9.
  8. ↑ Mandell, Gerald L.; Bennett, John E. (John Eugene); Dolin, Raphael. (2010). Mandell, Douglas, and Bennett's principles and practice of infectious disease. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0-443-06839-9.
  9. ↑ Mandell, Gerald L.; Bennett, John E. (John Eugene); Dolin, Raphael. (2010). Mandell, Douglas, and Bennett's principles and practice of infectious disease. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0-443-06839-9.
  10. ↑ Mandell, Gerald L.; Bennett, John E. (John Eugene); Dolin, Raphael. (2010). Mandell, Douglas, and Bennett's principles and practice of infectious disease. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0-443-06839-9.
  11. ↑ Mandell, Gerald L.; Bennett, John E. (John Eugene); Dolin, Raphael. (2010). Mandell, Douglas, and Bennett's principles and practice of infectious disease. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0-443-06839-9.
  12. ↑ Mandell, Gerald L.; Bennett, John E. (John Eugene); Dolin, Raphael. (2010). Mandell, Douglas, and Bennett's principles and practice of infectious disease. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0-443-06839-9.

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