Post by LymeEnigma on Jun 6, 2008 9:46:24 GMT -8
Brucellosis
Robert Rust Jr, MD, Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, University of Virginia School; Clinical and Residency Training, Child Neurology, University of Virginia Hospital and Clinics
Excerpt:
"Humoral immune mechanisms may participate in the control of acute infection, although the nature of that participation is not yet well understood. The capacity of humoral immune mechanisms to influence the course of the infectious reaction is likely limited because of the intracellular repose achieved by Brucella organisms. Nonetheless, the level of immunoglobulin M (IgM) antibodies begins to rise at the end of the first week of infection and usually peaks at approximately 1 month, when immunoglobulin G (IgG) antibodies begin to appear. The level of IgG antibodies often declines in the ensuing months, while IgM antibody titers may remain elevated for years. In some instances there is persistent elevation of IgG antibodies in association with chronic active infection. In other instances IgG a spike of IgG titers occurs after a phase of decline in concentration, suggesting a relapse of illness. Immunoglobulin A (IgA) antibodies are elaborated late and also may persist for very long intervals.
"Mediation of the most common neurological manifestations of acute brucellosis is not well understood. These are quite common, and consist of irritability, lethargy or lassitude, fatigue, headache, disturbances of mood, inattentiveness, anorexia, and sleep disturbance. These manifestations are not dissimilar from constitutional symptoms encountered in many other forms of systemic infectious disease. Some of them, specifically headache, anorexia, and mood and sleep disturbances, suggest that brainstem reticular and serotonergic pathways may be involved.
"Direct infection of the central nervous system (CNS) may play a role in these abnormalities. Some support for this conception is provided by the facts that, in some cases of acute brucellosis, Brucella organisms can be recovered from the cerebrospinal fluid (CSF) and that the spinal fluid, during the acute phase of illness, may exhibit pleocytosis, hypoglycorrhachia, and elevation of protein concentration. Because the organisms within the nervous system are chiefly in intracellular locations, they are recovered from cultures of spinal fluid in no more than 25% of cases. The likelihood of recovery of organisms from the blood is also only about 25%. The constitutional symptoms that occur in brucellosis suggest that an inflammatory reaction has been mounted against the invading organism, both within or outside the nervous system.
"By convention, these constitutional manifestations referable to the nervous system (lethargy, headache, depression, and so on) are not termed neurobrucellosis. Most instances of neurobrucellosis arise during the chronic phase of brucellosis. There are, however, cases in which neurobrucellosis does complicate acute brucellosis. When it does, it usually assumes the form of more profound degrees of encephalopathy or of a meningoencephalitic syndrome.
"Other forms of neurological dysfunction that may accompany the acute phase of brucellosis are hearing loss and peripheral neuritis. In regions where B melitensis is endemic, brucellosis may be the most common cause of acquired hearing loss, the onset of which may be during the acute, subacute, or chronic phase of disease. It is especially important, therefore, that we develop a better understanding of the cause of this complication."
*snip*
"In the decade of 1993-2002, at least one case was reported in 46 states, with 26 states recording a case in 2002. Although the number of cases is small, the highest annual incidence is in Wyoming. North Carolina (27 cases in 1993) and Arkansas (9 cases in 2001) experienced clusters of cases. States with the highest recent annual incidence (cases per million) are Wyoming (1.46), Texas (1.38), Hawaii (1.09), Arkansas (0.95), Arizona (0.92), California (0.83), Iowa (0.77), New Mexico (0.69), and Illinois (0.57) (Pappas, 2006)."
*snip*
Clinical manifestations of acute brucellosis
In most instances, the manifestations of acute brucellosis consist of a characteristic fever and various constitutional signs and symptoms, but few localizing features.
* The latency from infection to onset of symptoms of acute brucellosis is usually between 5 and 21 days, although occasionally the interval between infection and first symptoms is many months. The classic ensuing septicemic course is most likely to occur in regions of endemic disease and is usually due to B melitensis infection.
* The severity of the illness ranges from mild to seriously ill. Mild cases may last for just a few days, while the acute phase of severe cases may persist for weeks to many months. In some cases this lingering illness consists of fever and malaise, which occur in most cases. In some cases, severe debilitation may occur.
* Common manifestations of acute brucellosis include fever (80-90% of cases), chills, anorexia, insomnia, joint pain (60-80% of cases), bone pain (40-60% of cases), myalgia (20-70% of cases), profuse night sweats (20-25% of cases), and irritability (common).
* The fever of acute brucellosis caused by B melitensis usually lasts for 10-30 days, undulates irregularly, and is not associated with rash.
o Some very severe cases are termed malariform brucellosis because the undulating fever spikes reach very high temperatures and are associated with chills, drenching sweats, and prostration from the very onset of illness.
o The irregular undulation of fever spikes distinguishes malariform acute brucellosis from malaria, which produces quite regular fever spikes; the periodicity of malaria fever spikes (eg, tertiary, quaternary) is determined by the type of malarial parasite that has infected the host.
o Fever and other constitutional manifestations of acute brucellosis tend to be more severe and persistent in patients who attempt to remain active. Severity and duration typically are reduced by enforced bedrest.
o Classic acute septicemic presentations of brucellosis are very uncommon in North America and other regions in which the disease is not endemic.
* Some patients manifest focal abnormalities during acute brucellosis.
o The most common focal manifestation of acute brucellosis is pain, usually localized to the lower spine, paraspinous muscles, or upper buttocks. In some cases, neuralgic pain is distributed along lumbosacral peripheral nerves, especially the sciatic. The region of the lumbosacral vertebrae may be tender to percussion, as may the course of the sciatic nerve. Thus, these clinical features may closely resemble sciatica. The costovertebral joints may be similarly afflicted.
o Occasionally, patients develop pain, tenderness, swelling of joints (often monoarticular, knees more than elbows) or bone ends.
o Skin ulcerations, purpura, erythema, or petechiae may be found, from which organisms may at times be cultured. Some of these changes, especially the purpura, arise as consequences of immune-mediated thrombocytopenia.
o Abdominal discomfort or pain may be associated with anorexia and weight loss. The pain may in some instances suggest an acute abdomen. In instances where there is right upper quadrant pain, hepatic abscess must be excluded, especially if associated jaundice is present.
o In some cases, tender enlargement of the spleen is discerned.
o Some patients develop constipation.
o In some instances, tender enlargement of the testicles due to epididymo-orchitis, resembling mumps orchitis, develops after the first few days of high fever and chills or chilliness. Although it can be painfully persistent for a number of days, unlike mumps orchitis or brucellosis in sheep or goats, it seldom leads to sterility in humans.
o Urethritis or urinary tract infection may be found. Occasionally, the kidneys are involved, although the disease seldom results in renal failure.
* Unlike brucellosis of cattle, human acute brucellosis does not appear to carry any higher risk for abortion than any other form of bacteremic illness.
* Rarely, some severe varieties of focal involvement of nonneurological organ systems may occur as complications of acute brucellosis, complications that may secondarily injure the nervous system during the acute or ensuing chronic phase of brucellosis. These complications tend to arise in patients who are quite ill.
o Patients may develop such pulmonary complications as pleuritis or pneumonia, causing shortness of breath, pleuritic chest pain, and considerable fatigue. These complications are more common during the chronic phase of brucellosis.
o Rarely, bacterial endocarditis develops in patients who are very ill with acute brucellosis, causing chest pain, weight loss, severe fatigue, and various cardiopulmonary findings. Much more commonly, subacute brucellotic endocarditis arises during the chronic phase of brucellosis.
* The neurological manifestations of acute brucellosis include constitutional complaints (very common) and focal neurological disorders (rare).
o Nonfocal neurological manifestations of acute brucellosis include headache, irritability, lethargy, depression, disturbed consciousness and concentration, anorexia, and disturbed sleep.
o Headache, waxing and waning over a considerable period, may be the only sign of acute brucellosis, with symptoms suggesting migraine.
* The neurological syndrome most likely to arise in the acute phase is encephalopathy, with or without evidence of meningeal irritation.
o Encephalopathic acute brucellosis is most likely to arise with B melitensis infection.
o Mental status changes in acute brucellosis range along a continuum that includes irritability, confusion, obtundation, and coma.
o When an encephalopathic syndrome arises during acute brucellosis, it may evolve gradually over weeks to months. During this period, findings may wax and wane. This evolution tends to blur the distinction between acute and chronic brucellosis.
o In some patients with an encephalopathic form of acute brucellosis, the evolution may suggest development of MS or other chronic inflammatory diseases of the CNS.
o Some patients with encephalopathic acute brucellosis manifest meningismus, seizures, or CSF pleocytosis, suggesting acute meningitis or meningoencephalitis.
o Some patients with acute brucellosis have mild or more marked problems with language or memory.
* Sensorineural hearing loss is the second most common focal neurological abnormality to develop in the wake of acute brucellosis; it is localized to the vestibuloacoustic nerve.
* Rarely, neurological complications such as stroke or abscess may complicate brucellar endocarditis when the complication develops during the acute phase of brucellosis.
* Rare instances of hemiparesis complicating acute brucellosis have been described, some of which are due to brucellar endocarditis.
* Inflammatory pituitary abscess has been described in patients with acute brucellosis.
* Elevation of intracranial pressure rarely complicates acute brucellosis.
* Some patients have very mild courses of acute brucellosis, without strong suggestion of a septicemic course.
o Findings consist chiefly of fever and malaise suggestive of influenza, without any additional focal complaints.
o The long duration of fever and malaise, which may persist for 3 months or more, usually distinguishes brucellosis from influenza and many other febrile viral illnesses.
o Low-grade, long-term exposure to Brucella organisms is especially likely to engender mild brucellosis, hence this form of disease is seen in regions of endemic disease as well as in veterinarians and some individuals with occupational animal exposure in regions in which the disease is not endemic.
Subacute brucellosis is distinguished from mild acute brucellosis by its more insidious onset, but this distinction is not always clear; hence, these 2 types of brucellosis exist on a continuum.
* Subacute brucellosis does not have discrete onset of undulating fevers and does not produce marked constitutional symptoms.
* Low-grade fevers, aches and pains, and malaise are noted, but are relatively mild, resembling mild cases of influenza; their course persists for 10-13 days (in some cases many weeks, longer than is typical for influenza.
o As with mild acute brucellosis, the subacute form is most likely to be engendered by long-term, low-grade exposure to Brucella organisms, hence this form arises in some veterinarians or individuals with occupational exposure to herd animals.
o As with mild acute brucellosis, B abortus or B suis infection is more likely than B melitensis infections to cause of subacute brucellosis.
* Chronic brucellosis develops in the wake of some, but not all, subacute cases.
* In some instances, the development of neurological abnormalities is the first definite evidence that an individual is experiencing subacute brucellosis. These neurological abnormalities may evolve over time into a chronic form of brucellosis.
* Brucella-related deafness is among the most common of the neurological consequences of subacute brucellosis in regions of endemic disease.
* Note that some patients with findings suggestive of subacute brucellosis are actually experiencing manifestations of a nonbrucellotic "chronic fatigue syndrome" or are manifesting psychologically induced complaints.
o Brucella titers must be interpreted cautiously in attempting to distinguish brucellotic from psychogenic complaints in patients who are resident in areas of endemic disease, because of the high seroprevalence of anti-Brucella antibodies even in patients who have not manifested actual brucellosis.
Full article: www.emedicine.com/neuro/topic42.htm
Robert Rust Jr, MD, Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, University of Virginia School; Clinical and Residency Training, Child Neurology, University of Virginia Hospital and Clinics
Excerpt:
"Humoral immune mechanisms may participate in the control of acute infection, although the nature of that participation is not yet well understood. The capacity of humoral immune mechanisms to influence the course of the infectious reaction is likely limited because of the intracellular repose achieved by Brucella organisms. Nonetheless, the level of immunoglobulin M (IgM) antibodies begins to rise at the end of the first week of infection and usually peaks at approximately 1 month, when immunoglobulin G (IgG) antibodies begin to appear. The level of IgG antibodies often declines in the ensuing months, while IgM antibody titers may remain elevated for years. In some instances there is persistent elevation of IgG antibodies in association with chronic active infection. In other instances IgG a spike of IgG titers occurs after a phase of decline in concentration, suggesting a relapse of illness. Immunoglobulin A (IgA) antibodies are elaborated late and also may persist for very long intervals.
"Mediation of the most common neurological manifestations of acute brucellosis is not well understood. These are quite common, and consist of irritability, lethargy or lassitude, fatigue, headache, disturbances of mood, inattentiveness, anorexia, and sleep disturbance. These manifestations are not dissimilar from constitutional symptoms encountered in many other forms of systemic infectious disease. Some of them, specifically headache, anorexia, and mood and sleep disturbances, suggest that brainstem reticular and serotonergic pathways may be involved.
"Direct infection of the central nervous system (CNS) may play a role in these abnormalities. Some support for this conception is provided by the facts that, in some cases of acute brucellosis, Brucella organisms can be recovered from the cerebrospinal fluid (CSF) and that the spinal fluid, during the acute phase of illness, may exhibit pleocytosis, hypoglycorrhachia, and elevation of protein concentration. Because the organisms within the nervous system are chiefly in intracellular locations, they are recovered from cultures of spinal fluid in no more than 25% of cases. The likelihood of recovery of organisms from the blood is also only about 25%. The constitutional symptoms that occur in brucellosis suggest that an inflammatory reaction has been mounted against the invading organism, both within or outside the nervous system.
"By convention, these constitutional manifestations referable to the nervous system (lethargy, headache, depression, and so on) are not termed neurobrucellosis. Most instances of neurobrucellosis arise during the chronic phase of brucellosis. There are, however, cases in which neurobrucellosis does complicate acute brucellosis. When it does, it usually assumes the form of more profound degrees of encephalopathy or of a meningoencephalitic syndrome.
"Other forms of neurological dysfunction that may accompany the acute phase of brucellosis are hearing loss and peripheral neuritis. In regions where B melitensis is endemic, brucellosis may be the most common cause of acquired hearing loss, the onset of which may be during the acute, subacute, or chronic phase of disease. It is especially important, therefore, that we develop a better understanding of the cause of this complication."
*snip*
"In the decade of 1993-2002, at least one case was reported in 46 states, with 26 states recording a case in 2002. Although the number of cases is small, the highest annual incidence is in Wyoming. North Carolina (27 cases in 1993) and Arkansas (9 cases in 2001) experienced clusters of cases. States with the highest recent annual incidence (cases per million) are Wyoming (1.46), Texas (1.38), Hawaii (1.09), Arkansas (0.95), Arizona (0.92), California (0.83), Iowa (0.77), New Mexico (0.69), and Illinois (0.57) (Pappas, 2006)."
*snip*
Clinical manifestations of acute brucellosis
In most instances, the manifestations of acute brucellosis consist of a characteristic fever and various constitutional signs and symptoms, but few localizing features.
* The latency from infection to onset of symptoms of acute brucellosis is usually between 5 and 21 days, although occasionally the interval between infection and first symptoms is many months. The classic ensuing septicemic course is most likely to occur in regions of endemic disease and is usually due to B melitensis infection.
* The severity of the illness ranges from mild to seriously ill. Mild cases may last for just a few days, while the acute phase of severe cases may persist for weeks to many months. In some cases this lingering illness consists of fever and malaise, which occur in most cases. In some cases, severe debilitation may occur.
* Common manifestations of acute brucellosis include fever (80-90% of cases), chills, anorexia, insomnia, joint pain (60-80% of cases), bone pain (40-60% of cases), myalgia (20-70% of cases), profuse night sweats (20-25% of cases), and irritability (common).
* The fever of acute brucellosis caused by B melitensis usually lasts for 10-30 days, undulates irregularly, and is not associated with rash.
o Some very severe cases are termed malariform brucellosis because the undulating fever spikes reach very high temperatures and are associated with chills, drenching sweats, and prostration from the very onset of illness.
o The irregular undulation of fever spikes distinguishes malariform acute brucellosis from malaria, which produces quite regular fever spikes; the periodicity of malaria fever spikes (eg, tertiary, quaternary) is determined by the type of malarial parasite that has infected the host.
o Fever and other constitutional manifestations of acute brucellosis tend to be more severe and persistent in patients who attempt to remain active. Severity and duration typically are reduced by enforced bedrest.
o Classic acute septicemic presentations of brucellosis are very uncommon in North America and other regions in which the disease is not endemic.
* Some patients manifest focal abnormalities during acute brucellosis.
o The most common focal manifestation of acute brucellosis is pain, usually localized to the lower spine, paraspinous muscles, or upper buttocks. In some cases, neuralgic pain is distributed along lumbosacral peripheral nerves, especially the sciatic. The region of the lumbosacral vertebrae may be tender to percussion, as may the course of the sciatic nerve. Thus, these clinical features may closely resemble sciatica. The costovertebral joints may be similarly afflicted.
o Occasionally, patients develop pain, tenderness, swelling of joints (often monoarticular, knees more than elbows) or bone ends.
o Skin ulcerations, purpura, erythema, or petechiae may be found, from which organisms may at times be cultured. Some of these changes, especially the purpura, arise as consequences of immune-mediated thrombocytopenia.
o Abdominal discomfort or pain may be associated with anorexia and weight loss. The pain may in some instances suggest an acute abdomen. In instances where there is right upper quadrant pain, hepatic abscess must be excluded, especially if associated jaundice is present.
o In some cases, tender enlargement of the spleen is discerned.
o Some patients develop constipation.
o In some instances, tender enlargement of the testicles due to epididymo-orchitis, resembling mumps orchitis, develops after the first few days of high fever and chills or chilliness. Although it can be painfully persistent for a number of days, unlike mumps orchitis or brucellosis in sheep or goats, it seldom leads to sterility in humans.
o Urethritis or urinary tract infection may be found. Occasionally, the kidneys are involved, although the disease seldom results in renal failure.
* Unlike brucellosis of cattle, human acute brucellosis does not appear to carry any higher risk for abortion than any other form of bacteremic illness.
* Rarely, some severe varieties of focal involvement of nonneurological organ systems may occur as complications of acute brucellosis, complications that may secondarily injure the nervous system during the acute or ensuing chronic phase of brucellosis. These complications tend to arise in patients who are quite ill.
o Patients may develop such pulmonary complications as pleuritis or pneumonia, causing shortness of breath, pleuritic chest pain, and considerable fatigue. These complications are more common during the chronic phase of brucellosis.
o Rarely, bacterial endocarditis develops in patients who are very ill with acute brucellosis, causing chest pain, weight loss, severe fatigue, and various cardiopulmonary findings. Much more commonly, subacute brucellotic endocarditis arises during the chronic phase of brucellosis.
* The neurological manifestations of acute brucellosis include constitutional complaints (very common) and focal neurological disorders (rare).
o Nonfocal neurological manifestations of acute brucellosis include headache, irritability, lethargy, depression, disturbed consciousness and concentration, anorexia, and disturbed sleep.
o Headache, waxing and waning over a considerable period, may be the only sign of acute brucellosis, with symptoms suggesting migraine.
* The neurological syndrome most likely to arise in the acute phase is encephalopathy, with or without evidence of meningeal irritation.
o Encephalopathic acute brucellosis is most likely to arise with B melitensis infection.
o Mental status changes in acute brucellosis range along a continuum that includes irritability, confusion, obtundation, and coma.
o When an encephalopathic syndrome arises during acute brucellosis, it may evolve gradually over weeks to months. During this period, findings may wax and wane. This evolution tends to blur the distinction between acute and chronic brucellosis.
o In some patients with an encephalopathic form of acute brucellosis, the evolution may suggest development of MS or other chronic inflammatory diseases of the CNS.
o Some patients with encephalopathic acute brucellosis manifest meningismus, seizures, or CSF pleocytosis, suggesting acute meningitis or meningoencephalitis.
o Some patients with acute brucellosis have mild or more marked problems with language or memory.
* Sensorineural hearing loss is the second most common focal neurological abnormality to develop in the wake of acute brucellosis; it is localized to the vestibuloacoustic nerve.
* Rarely, neurological complications such as stroke or abscess may complicate brucellar endocarditis when the complication develops during the acute phase of brucellosis.
* Rare instances of hemiparesis complicating acute brucellosis have been described, some of which are due to brucellar endocarditis.
* Inflammatory pituitary abscess has been described in patients with acute brucellosis.
* Elevation of intracranial pressure rarely complicates acute brucellosis.
* Some patients have very mild courses of acute brucellosis, without strong suggestion of a septicemic course.
o Findings consist chiefly of fever and malaise suggestive of influenza, without any additional focal complaints.
o The long duration of fever and malaise, which may persist for 3 months or more, usually distinguishes brucellosis from influenza and many other febrile viral illnesses.
o Low-grade, long-term exposure to Brucella organisms is especially likely to engender mild brucellosis, hence this form of disease is seen in regions of endemic disease as well as in veterinarians and some individuals with occupational animal exposure in regions in which the disease is not endemic.
Subacute brucellosis is distinguished from mild acute brucellosis by its more insidious onset, but this distinction is not always clear; hence, these 2 types of brucellosis exist on a continuum.
* Subacute brucellosis does not have discrete onset of undulating fevers and does not produce marked constitutional symptoms.
* Low-grade fevers, aches and pains, and malaise are noted, but are relatively mild, resembling mild cases of influenza; their course persists for 10-13 days (in some cases many weeks, longer than is typical for influenza.
o As with mild acute brucellosis, the subacute form is most likely to be engendered by long-term, low-grade exposure to Brucella organisms, hence this form arises in some veterinarians or individuals with occupational exposure to herd animals.
o As with mild acute brucellosis, B abortus or B suis infection is more likely than B melitensis infections to cause of subacute brucellosis.
* Chronic brucellosis develops in the wake of some, but not all, subacute cases.
* In some instances, the development of neurological abnormalities is the first definite evidence that an individual is experiencing subacute brucellosis. These neurological abnormalities may evolve over time into a chronic form of brucellosis.
* Brucella-related deafness is among the most common of the neurological consequences of subacute brucellosis in regions of endemic disease.
* Note that some patients with findings suggestive of subacute brucellosis are actually experiencing manifestations of a nonbrucellotic "chronic fatigue syndrome" or are manifesting psychologically induced complaints.
o Brucella titers must be interpreted cautiously in attempting to distinguish brucellotic from psychogenic complaints in patients who are resident in areas of endemic disease, because of the high seroprevalence of anti-Brucella antibodies even in patients who have not manifested actual brucellosis.
Full article: www.emedicine.com/neuro/topic42.htm