Virus associated meningitisPolio Virus

Dr. Hala Al Daghistani

The most important Enteroviruses are the three poliovirus serotypes (types 1, 2, and 3). Improvement of sanitary conditions tends to impede spread of the viruses Transmitted with contaminated food and water

Pathogenesis The particular tropism of polioviruses for the CNS, which they usually reach by passage

across the blood–CNS barrier, is perhaps favored by reflex dilatation of capillaries supplying the affected motor centers of the anterior horn of the brainstem or spinal cord.

Motor neurons are particularly vulnerable to infection and variable degrees of neuronal destruction.

The mouth is the portal of entry of the virus, and primary multiplication takes place in the oropharynx or intestine. The virus is regularly present in the throat and in the stools before the onset of illness. One week after infection, there is little virus in the throat, but virus continues to be excreted in the stools for several weeks even though high antibody levels are present in the blood. The virus may be found in the blood of patients with nonparalytic poliomyelitis. The CNS may then be invaded by way of the circulating blood. Poliovirus can spread along axons of peripheral nerves to the CNS, where it continues to progress along the fibers of the lower motor neurons to involve the spinal cord or the brain. Poliovirus invades certain types of nerve cells, and in the process of its intracellular multiplication, it may damage or completely destroy these cells. Poliovirus does not multiply in muscle in vivo. The changes that occur in peripheral nerves and voluntary muscles are secondary to the destruction of nerve cells.

Clinical Manifestations Most infections (perhaps 90%) are either completely subclinical or so mild that they do

not come to attention. When disease does result, the incubation period ranges usually between 7 and 14 days.

Three types of disease can be observed. Abortive poliomyelitis is a nonspecific febrile illness of 2- to 3-day duration with no

signs of CNS localization.

Aseptic meningitis (nonparalytic poliomyelitis) is characterized by signs of meningeal irritation (stiff neck, pain, and stiffness in the back) in addition to the signs of abortive poliomyelitis; recovery is rapid and complete, usually within a few days. (The nerve cells involved are not sufficient in number to result in clinically evident weakness)

Paralytic poliomyelitis , occurs in less than 2% of infections. It is the major possible outcome of infection and is often preceded by a period of minor illness. There are signs of meningeal irritation, but the hallmark of paralytic poliomyelitis is asymmetric flaccid paralysis. (Here large numbers of the nerve cells are rendered useless and the muscles which they innervate are unable to cause motion).

The extent of involvement varies greatly from case to case; however, in its most serious forms, all four limbs may be completely paralyzed or the brainstem may be attacked, with paralysis of the cranial nerves and muscles of respiration.

PREVENTIONTwo types of poliovirus vaccines are currently licensed (Each contains all three viral serotypes).

I. Inactivated polio vaccine (SALK) IPV (two doses 6–8 weeks apart and the third 8–12 months later) produces antibody responses in more than 98% of recipients

I. live oral attenuated virus vaccine (SABIN). Oral polio vaccine (OPV) is composed of live, attenuated viruses that have undergone serial passage in cell cultures. (three doses, the first two doses usually 6–8 weeks apart and the third 8–12 months later, and produces

antibodies to all three serotypes in more than 95% of recipients; these antibodies, persist for several years). As with IPV, recall boosters are recommended to maintain adequate antibody levels. Like wild poliovirus, OPV viruses infect and replicate in the oropharynx and intestinal tract and can be spread to other persons. One disadvantage of OPV is the remote risk of vaccine-associated paralytic disease in some recipients, including immunocompromised persons.

Cryptococcus sppCryptococcus neoformans

Dr. Hala Al Daghistani

Cryptococcus neoformans is a yeast that produces a characteristic capsule, extending the overall diameter to 25 _m or more. This capsule is unique among pathogenic fungi and is a complex polysaccharide polymer, the major component of which is Glucuronoxylomannan (GXM). Capsule production varies by strain and with environmental conditions. C. neoformans grows at 35 to 37°C on a variety of common media, including blood agar, chocolate agar, and Sabouraud’s agar. Mucoid, bacteria-like colonies are produced in 2 to 3 days. In addition to the capsule, extracellular products include a urease enzyme and melanin pigment. The sexual state of C. neoformans places it in the Basidiomycetes

CryptococcosisC. neoformans is found throughout the world, particularly in soil contaminated with pigeon or other bird droppings. The birds themselves are not ill. The cryptococci in the soil produce few or no capsules, which makes them more readily aerosolized.

Inhalation of yeast cells from these sites is the presumed mode of transmission.

The primary disease caused by cryptococci is a chronic meningitis. The onset is slow, with low-grade fever and headache progressing to altered mental state and seizures.

In the cerebrospinal fluid (CSF) and in tissues, the inflammatory response is often remarkably muted. Most patients have some obvious form of immune compromise, although some show no demonstrable immune defect.

Cryptococcosis in immunocompromised patients occurs primarily in those with defects in T-lymphocyte function, or in those treated with immunosuppressive agents (eg, steroids).

Case-to-case transmission has not been documented.

PathogenesisFollowing inhalation, the yeast begins to overproduce the polysaccharide capsule, which determines virulence. The capsule is antiphagocytic and has a number of other immunomodulating effects.

The GXM is able to bind complement components while at the same time reducing the ability of PMNs and macrophages to phagocytose and kill cryptococci. This may be due to the combination of the massive size of the capsule and the way in which it binds C3. There is also evidence that the capsule can interfere with antigen presentation and the development of T cell–mediated immune processes.At this stage the organism has a strong affinity for the central nervous system (CNS), possibly due to its C3 binding and the relatively low levels of complement found there.Cryptococci produce enough capsule that the GXM can be readily detected in the blood and other body fluids. This circulating polysaccharide is able to

1. down regulate immune responses, particularly the development of protective TH1-type mediators

2. suppression of the specific antibody response.

Cryptococci are also able to oxidize exogenous catecholamines to produce melanin, a process that may protect them from the oxidative injury of phagocytes.Tissue reaction to C.neoformans varies from little or none to purulent or granulomatous.Anticryptococcal antibody and complement do not directly damage the organism but may be a key component in the development of cellular host defense mechanisms and the clearance of circulating antigen.

Cryptococcosis : Clinical aspectsMeningitis is the most commonly recognized form of cryptococcal disease; it usually has

a slow, insidious onset with relatively nonspecific findings until late in its course. Intermittent headache, irritability, dizziness, and difficulty with complex cerebral functions appear over weeks or months. Fever is usually present. Seizures, cranial nerve signs, and papilledema may appear later in the clinical course, as may dementia and decreased levels of consciousness.

DiagnosisTypical cerebrospinal fluid (CSF) findings in cryptococcal meningitis are increased pressure, pleocytosis (usually more than 100 cells) with predominance of lymphocytes, and depression of glucose levels. In some cases, one or all of these findings may be absent, yet cryptococci are isolated on culture.

Cryptococcal capsules are demonstrable in CSF in roughly 50% of cases by mixing centrifuged sediment with India ink and examining the mixture under the microscope.

In the isolation of C. neoformans, the volume of CSF sampled is important. The number of organisms present may be small enough to require a substantial volume of fluid (30 mL) to yield a positive culture.

If cryptococcosis is suspected and cultures are negative, detection of the GXM polysaccharide antigen in the CSF or serum by latex agglutination or enzyme immunoassay methods is recommended. These tests are very sensitive and specific, and

their quantitation has prognostic significance. A rising antigen level indicates progression and a declining titer is a favorable sign.