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If suspected, fungal meningitis is diagnosed by testing blood and CSF samples for pathogens. Identifying the specific pathogen is necessary to determine the proper course of treatment and the prognosis. Measurement of opening pressure, cell count with differential, glucose and protein concentrations, Gram's stain, India ink, and culture tests should be preformed on CSF samples when fungal meningitis is suspected.
Prognosis depends on the pathogen responsible for the infection and risk group. Overall mortality for "Candida" meningitis is 10-20%, 31% for patients with HIV, and 11% in neurosurgical cases (when treated). Prognosis for "Aspergillus" and coccidioidal infections is poor.
Babies born from mothers with symptoms of Herpes Simplex Virus (HSV) should be tested for viral infection. Liver tests, complete blood count (CBC), cerebrospinal fluid analyses, and chest X-ray should all be completed to diagnose meningitis. Samples should be taken from skin, conjunctiva (eye), mouth and throat, rectum, urine, and the CSF for viral culture and PCR analysis with respect to the sample from CSF.
A lumbar puncture (LP) is necessary to diagnose meningitis. Cerebrospinal fluid (CSF) culture is the most important study for the diagnosis of neonatal bacterial meningitis because clinical signs are non-specific and unreliable. Blood cultures may be negative in 15-55% of cases, deeming it unreliable as well. However, a CSF/blood glucose ratio below two-thirds has a strong relationship to bacterial meningitis. A LP should be done in all neonates with suspected meningitis, with suspected or proven sepsis (whole body inflammation) and should be considered in all neonates in whom sepsis is a possibility. The role of the LP in neonates who are healthy appearing but have maternal risk factors for sepsis is more controversial; the yield of the LP in these patients may be low.
Early-onset is deemed when infection is within one week of birth. Late-onset is deemed after the first week.
This is a group of tests that use polymerase chain reaction (PCR) to detect mycobacterial nucleic acid. These test vary in which nucleic acid sequence they detect and vary in their accuracy. The two most common commercially available tests are the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe) and Amplicor. In 2007, review concluded that for diagnosing tuberculous meningitis "Individually, the AMTD test appears to perform the best (sensitivity 74% and specificity 98%)", they found the pooled prevalence of TB meningitis to be 29%.
Dependent on the infectious syndrome, symptoms include fever, fatigue, dry cough, headache, blurred vision, and confusion. Symptom onset is often subacute, progressively worsened over several weeks. The two most common presentations are meningitis (an infection in and around the brain) and pulmonary (lung) infection.
Detection of cryptococcal antigen (capsular material) by culture of CSF, sputum and urine provides definitive diagnosis. Blood cultures may be positive in heavy infections. India ink of the CSF is a traditional microscopic method of diagnosis, although the sensitivity is poor in early infection, and may miss 15-20% of patients with culture-positive cryptococcal meningitis. Unusual morphological forms are rarely seen. Cryptococcal antigen from cerebrospinal fluid is the best test for diagnosis of cryptococcal meningitis in terms of sensitivity. Apart from conventional methods of detection like direct microscopy and culture, rapid diagnostic methods to detect cryptococcal antigen by latex agglutination test, lateral flow immunochromatographic assay (LFA), or enzyme immunoassay (EIA). A new cryptococcal antigen LFA was FDA approved in July 2011. Polymerase chain reaction (PCR) has been used on tissue specimens.
Cryptococcosis can rarely occur in the non-immunosuppressed people, particularly with "Cryptococcus gattii".
Diagnosis of TB meningitis is made by analysing cerebrospinal fluid collected by lumbar puncture. When collecting CSF for suspected TB meningitis, a minimum of 1ml of fluid should be taken (preferably 5 to 10ml). The CSF usually has a high protein, low glucose and a raised number of lymphocytes. Acid-fast bacilli are sometimes seen on a CSF smear, but more commonly, "M. tuberculosis" is grown in culture. A spiderweb clot in the collected CSF is characteristic of TB meningitis, but is a rare finding. ELISPOT testing is not useful for the diagnosis of acute TB meningitis and is often false negative, but may paradoxically become positive after treatment has started, which helps to confirm the diagnosis.
Cryptococcosis is a very subacute infection with a prolonged subclinical phase lasting weeks to months in persons with HIV/AIDS before the onset of symptomatic meningitis. In Sub-Saharan Africa, the prevalence rates of detectable cryptococcal antigen in peripheral blood is often 4–12% in persons with CD4 counts lower than 100 cells/mcL.
Cryptococcal antigen screen and preemptive treatment with fluconazole is cost saving to the healthcare system by avoiding cryptococcal meningitis. The World Health Organization recommends cryptococcal antigen screening in HIV-infected persons entering care with CD4<100 cells/μL. This undetected subclinical cryptococcal (if not preemptively treated with anti-fungal therapy) will often go on to develop cryptococcal meningitis, despite receiving HIV therapy. Cryptococcosis accounts for 20-25% of the mortality after initiating HIV therapy in Africa. What is effective preemptive treatment is unknown, with the current recommendations on dose and duration based on expert opinion. Screening in the United States is controversial, with official guidelines not recommending screening, despite cost-effectiveness and a 3% U.S. cryptococcal antigen prevalence in CD4<100 cells/μL.
Meningitis can be diagnosed after death has occurred. The findings from a post mortem are usually a widespread inflammation of the pia mater and arachnoid layers of the meninges. Neutrophil granulocytes tend to have migrated to the cerebrospinal fluid and the base of the brain, along with cranial nerves and the spinal cord, may be surrounded with pus – as may the meningeal vessels.
A lumbar puncture is done by positioning the person, usually lying on the side, applying local anesthetic, and inserting a needle into the dural sac (a sac around the spinal cord) to collect cerebrospinal fluid (CSF). When this has been achieved, the "opening pressure" of the CSF is measured using a manometer. The pressure is normally between 6 and 18 cm water (cmHO); in bacterial meningitis the pressure is usually elevated. In cryptococcal meningitis, intracranial pressure is markedly elevated. The initial appearance of the fluid may prove an indication of the nature of the infection: cloudy CSF indicates higher levels of protein, white and red blood cells and/or bacteria, and therefore may suggest bacterial meningitis.
The CSF sample is examined for presence and types of white blood cells, red blood cells, protein content and glucose level. Gram staining of the sample may demonstrate bacteria in bacterial meningitis, but absence of bacteria does not exclude bacterial meningitis as they are only seen in 60% of cases; this figure is reduced by a further 20% if antibiotics were administered before the sample was taken. Gram staining is also less reliable in particular infections such as listeriosis. Microbiological culture of the sample is more sensitive (it identifies the organism in 70–85% of cases) but results can take up to 48 hours to become available. The type of white blood cell predominantly present (see table) indicates whether meningitis is bacterial (usually neutrophil-predominant) or viral (usually lymphocyte-predominant), although at the beginning of the disease this is not always a reliable indicator. Less commonly, eosinophils predominate, suggesting parasitic or fungal etiology, among others.
The concentration of glucose in CSF is normally above 40% of that in blood. In bacterial meningitis it is typically lower; the CSF glucose level is therefore divided by the blood glucose (CSF glucose to serum glucose ratio). A ratio ≤0.4 is indicative of bacterial meningitis; in the newborn, glucose levels in CSF are normally higher, and a ratio below 0.6 (60%) is therefore considered abnormal. High levels of lactate in CSF indicate a higher likelihood of bacterial meningitis, as does a higher white blood cell count. If lactate levels are less than 35 mg/dl and the person has not previously received antibiotics then this may rule out bacterial meningitis.
Various other specialized tests may be used to distinguish between different types of meningitis. A latex agglutination test may be positive in meningitis caused by "Streptococcus pneumoniae", "Neisseria meningitidis", "Haemophilus influenzae", "Escherichia coli" and "group B streptococci"; its routine use is not encouraged as it rarely leads to changes in treatment, but it may be used if other tests are not diagnostic. Similarly, the limulus lysate test may be positive in meningitis caused by Gram-negative bacteria, but it is of limited use unless other tests have been unhelpful. Polymerase chain reaction (PCR) is a technique used to amplify small traces of bacterial DNA in order to detect the presence of bacterial or viral DNA in cerebrospinal fluid; it is a highly sensitive and specific test since only trace amounts of the infecting agent's DNA is required. It may identify bacteria in bacterial meningitis and may assist in distinguishing the various causes of viral meningitis (enterovirus, herpes simplex virus 2 and mumps in those not vaccinated for this). Serology (identification of antibodies to viruses) may be useful in viral meningitis. If tuberculous meningitis is suspected, the sample is processed for Ziehl-Neelsen stain, which has a low sensitivity, and tuberculosis culture, which takes a long time to process; PCR is being used increasingly. Diagnosis of cryptococcal meningitis can be made at low cost using an India ink stain of the CSF; however, testing for cryptococcal antigen in blood or CSF is more sensitive, particularly in people with AIDS.
A diagnostic and therapeutic difficulty is "partially treated meningitis", where there are meningitis symptoms after receiving antibiotics (such as for presumptive sinusitis). When this happens, CSF findings may resemble those of viral meningitis, but antibiotic treatment may need to be continued until there is definitive positive evidence of a viral cause (e.g. a positive enterovirus PCR).
The diagnosis of viral meningitis is made by clinical history, physical exam, and several diagnostic tests. Most importantly, cerebrospinal fluid (CSF) is collected via lumbar puncture (also known as spinal tap). This fluid, which normally surrounds the brain and spinal cord, is then analyzed for signs of infection. CSF findings that suggest a viral cause of meningitis include an elevated white blood cell count (usually 10-100 cells/µL) with a lymphocytic predominance in combination with a normal glucose level. Increasingly, cerebrospinal fluid PCR tests have become especially useful for diagnosing viral meningitis, with an estimated sensitivity of 95-100%. Additionally, samples from the stool, urine, blood and throat can also help to identify viral meningitis.
In certain cases, a CT scan of the head should be done before a lumbar puncture such as in those with poor immune function or those with increased intracranial pressure.
Chest x-rays rarely demonstrate nodules or cavities in the lungs, but these images commonly demonstrate lung opacification, pleural effusions, or enlargement of lymph nodes associated with the lungs. Computed tomography scans of the chest are better able to detect these changes than chest x-rays.
Due to the importance of disease caused by "S. pneumoniae" several vaccines have been developed to protect against invasive infection. The World Health Organization recommend routine childhood pneumococcal vaccination; it is incorporated into the childhood immunization schedule in a number of countries including the United Kingdom, United States, and South Africa.
Coccidioidomycosis diagnosis relies on a combination of an infected person's signs and symptoms, findings on radiographic imaging, and laboratory results.
The disease is commonly misdiagnosed as bacterial community-acquired pneumonia. The fungal infection can be demonstrated by microscopic detection of diagnostic cells in body fluids, exudates, sputum and biopsy tissue by methods of Papanicolaou or Grocott's methenamine silver staining. These stains can demonstrate spherules and surrounding inflammation.
With specific nucleotide primers, "C.immitis" DNA can be amplified by polymerase chain reaction (PCR). It can also be detected in culture by morphological identification or by using molecular probes that hybridize with "C.immitis" RNA. "C. immitis" and "C. posadasii" cannot be distinguished on cytology or by symptoms, but only by DNA PCR.
An indirect demonstration of fungal infection can be achieved also by serologic analysis detecting fungal antigen or host IgM or IgG antibody produced against the fungus. The available tests include the tube-precipitin (TP) assays, complement fixation assays, and enzyme immunoassays. TP antibody is not found in cerebrospinal fluid (CSF). TP antibody is specific and is used as a confirmatory test, whereas ELISA is sensitive and thus used for initial testing.
If the meninges are affected, CSF will show abnormally low glucose levels in CSF, an increased level of protein in the CSF, and lymphocytic pleocytosis. Rarely, CSF eosinophilia is present.
There are several methods to diagnose meningeal syphilis. One of the most common ways include visualizing the organisms by immunofluorescence and dark field microscopy. Dark field microscopy initially had the finding that the spirochete has a corkscrew appearance and that it is spirillar and gram (-) bacteria. Another method would also be through the screening test and serology. Serology includes two types of antibody test: Nontreponemal antibody test and Treponemal antibody test (specific test). The Nontreponemal antibody test screens with VDRL (Venereal Disease Research Lab) and RPR (Rapid Plasma Reagin). The Treponemal antibody test (specific test) confirms with FTA-ABS (Fluorescent treponemal antibody-absorption). Brain imaging and MRI scans may be used when diagnosing patients; however, they do not prove to be as effective as specific tests. Specific tests for treponemal antibody are typically more expensive because the earliest anitbodies bind to spirochetes. These tests are usually more specific and remain positive in patients with other treponemal diseases.
Fungal pneumonia can be diagnosed in a number of ways. The simplest and cheapest method is to culture the fungus from a patient's respiratory fluids. However, such tests are not only insensitive but take time to develop which is a major drawback because studies have shown that slow diagnosis of fungal pneumonia is linked to high mortality. Microscopy is another method but is also slow and imprecise. Supplementing these classical methods is the detection of antigens. This technique is significantly faster but can be less sensitive and specific than the classical methods.
A molecular test based on quantitative PCR is also available from Myconostica. Relying on DNA detection, this is the most sensitive and specific test available for fungi but it is limited to detecting only pneumocystis jirovecii and aspergillus.
Depending on the nature of infection an appropriate sample is collected for laboratory identification. Pneumococci are typically gram-positive cocci seen in pairs or chains. When cultured on blood agar plates with added optochin antibiotic disk they show alpha-hemolytic colonies and a clear zone of inhibition around the disk indicating sensitivity to the antibiotic. Pneumococci are also bile soluble. Just like other streptococci they are catalase-negative. A Quellung test can identify specific capsular polysaccharides.
Pneumococcal antigen (cell wall C polysaccharide) may be detected in various body fluids. Older detection kits, based on latex agglutination, added little value above Gram staining and were occasionally false-positive. Better results are achieved with rapid immunochromatography, which has a sensitivity (identifies the cause) of 70–80% and >90% specificity (when positive identifies the actual cause) in pneumococcal infections. The test was initially validated on urine samples but has been applied successfully to other body fluids. Chest X-rays can also be conducted to confirm inflammation though are not specific to the causative agent.
Animal pathogens exist as facultative parasites. They are an exceptionally rare cause of meningoencephalitis.
clinical diagnosis include recurrent or recent herpes infection fever, headache, mental symptom, convulsion, disturbance of consciousness, focal signs.
CSF ,EEG, CT, MRI are responsive to specific antivirus agent.
Definite diagnosis – besides the above, the followings are needed
CSF: HSV-antigen,HSV-Antibody, brain biopsy or pathology: Cowdry in intranuclear
CSF: the DNA of the HSV(PCR)
cerebral tissue or specimen of the CSF:HSV
except other viral encephalitis
Because the risk of meningococcal disease is increased among USA's military recruits, all military recruits routinely receive primary immunization against the disease.
Diagnosis starts by examining the patient's symptoms. Symptoms can vary. Symptoms can include headache, sensitivity to light, neck stiffness, nausea, and vomiting. In some patients, fever is absent. Neurological examination and MRI can be normal.
Mollaret's meningitis is suspected based on symptoms, and can be confirmed by HSV 1 or HSV 2 on PCR of Cerebrospinal fluid (CSF), although not all cases test positive on PCR. PCR is performed on spinal fluid or blood, however, the viruses do not need to enter the spinal fluid or blood to spread within the body: they can spread by moving through the axons and dendrites of the nerves.
During the first 24 h of the disease the spinal fluid will show predominant polymorphonuclear neutrophils and large cells that have been called endothelial (Mollaret’s) cells.
A study performed on patients who had diffuse symptoms, such as persistent or intermittent headaches, concluded that although PCR is a highly sensitive method for detection, it may not always be sensitive enough for identification of viral DNA in CSF, due to the fact that viral shedding from latent infection may be very low. The concentration of viruses in CSF during subclinical infection might be very low.
Investigations include blood tests (electrolytes, liver and kidney function, inflammatory markers and a complete blood count) and usually X-ray examination of the chest. The most important test in identifying or ruling out meningitis is analysis of the cerebrospinal fluid (fluid that envelops the brain and the spinal cord) through lumbar puncture (LP). However, if the patient is at risk for a cerebral mass lesion or elevated intracranial pressure (recent head injury, a known immune system problem, localizing neurological signs, or evidence on examination of a raised ICP), a lumbar puncture may be contraindicated because of the possibility of fatal brain herniation. In such cases, a CT or MRI scan is generally performed prior to the lumbar puncture to exclude this possibility. Otherwise, the CT or MRI should be performed after the LP, with MRI preferred over CT due to its superiority in demonstrating areas of cerebral edema, ischemia, and meningeal inflammation.
During the lumbar puncture procedure, the opening pressure is measured. A pressure of over 180 mm HO is suggestive of bacterial meningitis.
It is likely that Mollaret meningitis is underrecognized by physicians, and improved recognition may limit unwarranted antibiotic use and shorten or eliminate unnecessary hospital admission.
PCR testing has advanced the state of the art in research, but PCR can be negative in individuals with Mollaret's, even during episodes with severe symptoms. For example, Kojima et al. published a case study for an individual who was hospitalized repeatedly, and who had clinical symptoms including genital herpes lesions. However, the patient was sometimes negative for HSV-2 by PCR, even though his meningitis symptoms were severe. Treatment with acyclovir was successful, indicating that a herpes virus was the cause of his symptoms.
On chest X-ray and CT, pulmonary aspergillosis classically manifests as a halo sign, and, later, an air crescent sign.
In hematologic patients with invasive aspergillosis, the galactomannan test can make the diagnosis in a noninvasive way. False positive "Aspergillus" galactomannan tests have been found in patients on intravenous treatment with some antibiotics or fluids containing gluconate or citric acid such as some transfusion platelets, parenteral nutrition or PlasmaLyte.
On microscopy, "Aspergillus" species are reliably demonstrated by silver stains, e.g., Gridley stain or Gomori methenamine-silver. These give the fungal walls a gray-black colour. The hyphae of "Aspergillus" species range in diameter from 2.5 to 4.5 µm. They have septate hyphae, but these are not always apparent, and in such cases they may be mistaken for Zygomycota. "Aspergillus" hyphae tend to have dichotomous branching that is progressive and primarily at acute angles of about 45°.
It is recommended that primary immunization against meningococcal disease with meningitis A,C,Y and W-135 vaccines for all young adolescents at 11–12 years of age and all unvaccinated older adolescents at 15 years of age. Although conjugate vaccines are the preferred meningococcal vaccine in adolescents 11 years of age or older, polysaccharide vaccines are an acceptable alternative if the conjugated vaccine is unavailable.
Testing for miliary tuberculosis is conducted in a similar manner as for other forms of tuberculosis, although a number of tests must be conducted on a patient to confirm diagnosis. Tests include chest x-ray, sputum culture, bronchoscopy, open lung biopsy, head CT/MRI, blood cultures, fundoscopy, and electrocardiography. The tuberculosis (TB) blood test, also called an Interferon Gamma Release Assay or IGRA, is a way to diagnose latent TB.
A variety of neurological complications have been noted in miliary tuberculosis patients—tuberculous meningitis and cerebral tuberculomas being the most frequent. However, a majority of patients improve following antituberculous treatment. Rarely lymphangitic spread of lung cancer could mimic miliary pattern of tuberculosis on regular chest X-ray.
The tuberculin skin test, commonly used for detection of other forms of tuberculosis, is not useful in the detection of miliary tuberculosis. The tuberculin skin test fails due to the high numbers of false negatives. These false negatives may occur because of higher rates of tuberculin anergy compared to other forms of tuberculosis.
It has been proposed that viral meningitis might lead to inflammatory injury of the vertebral artery wall.
The Meningitis Research Foundation is conducting a study to see if new genomic techniques can the speed, accuracy and cost of diagnosing meningitis in children in the UK. The research team will develop a new method to be used for the diagnosis of meningitis, analysing the genetic material of microorganisms found in CSF (cerebrospinal fluid). The new method will first be developed using CSF samples where the microorganism is known, but then will be applied to CSF samples where the microorganism is unknown (estimated at around 40%) to try and identify a cause.
The most popular treatment forms for any type of syphilis uses penicillin, which has been an effective treatment used since the 1940s.
Other forms also include Benzathine penicillin, which is usually used for primary and secondary syphilis (it has no resistance to penicillin however). Benzathine penicillin is used for long acting form, and if conditions worsen, penicillin G is used for late syphilis.