Wednesday, April 18, 2012

(I) Septic meningitis Septic meningitis is an inflammation of the meninges caused by bacterial pathogens . Acute meningitis is usually bacterial infection caused by one of several organisms. For development of septic (bacterial) meningitis , the invading organism must gain access to the subarachnoid space (Ashwal ; 1995 ). (A) Pathophysiology : After initial colonization in the upper respiratory tract the invading organism can gain access to the subarachnoid space usually via haematogenous spread and less frequently through an injury such as skull fracture which can cause meningeal seeding via direct bacterial inoculation during trauma (Johansson & Bergentoft ,2005). Bacterial meningitis in the newborn is transmitted either vertically from colonized pathogens in the maternal intestinal or genital tract or horizontally from nursery personnel or other contacts with the patient (Kelley ; 1996).Once bacteria reached to the CSF the relative lack of antibody, complement and white blood cells (WBCs) allow the bacterial infection to flourish (Waler & Rathore; 1995). The types of bacteria that cause septic meningitis vary according to the age of patients. In premature babies and newborn up to three months, the commonest bacteria are group B streptococcus especially in the first week of life–and bacteria that normally inhabit the digestive tract such as Escherichia coli. Listeria monocytogenes may affect the newborn and occurs in epidemics ( Sáez-Llorens & McCracken , 2003). Older children are more commonly affected by Neisseria meningitidis , Streptococcus pneumonia and Haemophilus influenza type B (Ginsberg ,2004). In adults, N. meningitidis and S. pneumonia together cause 80% of all cases of meningitis with increased risk of L. monocytogenes in those over 50 years. Staphylococci , Pseudomonas and other Gram-negative bacilli are likely to cause meningitis especially in patients with trauma, neurosurgical interferences and with impaired immune system (van de Beek et al ., 2006 & Tunkel et al ., 2004 ). ( B) Symptoms and signs : The history in children with bacterial meningitis varies with age. The younger the child, the less likely to exhibit the classical symptoms which include fever, headache and meningeal signs. Babies under 3 months may have very non specific symptoms including hyper or hypothermia, changes in sleeping or eating habits, irritability or lethargy, vomiting, high pitched cry or seizures (Nigrovic et al ., 2007). According to Kelley;(1996) , signs of meningeal irritation are diagnostically helpful when present, they include: * Nuchal rigidity or discomfort on neck flexion. * Kernig's sign which is characterized by passive knee extension in supine patient elicits neck pain. * Brudziniski's sign which is characterized by passive neck , single or both hip flexion . * Meningismus and bulging fontanels may be seen. Other manifestations are systemic findings such as extracranial infection as sinusitis, otitis media, urinary tract infection , arthritis , non-branching pitechae, cutaneous hemorrhage and endotoxic shock especially with Neisseria meningitidis (Thomas et al., 2002) . (C) Risk factors : Risk factors include young age, rapid onset of illness, low peripheral WBCs count and high CSF protein (Pfister , 2005 ). (D) Prognosis : Prognosis depend on the virulence of pathogen , age and severity of acute illness (Puopolo et al ., 2005). In general, mortality rates vary with age and pathogen with the highest being for S. pneumonia. Bacterial meningitis also causes long-term sequelae and results in significant morbidity beyond the neonatal period. Mortality rates are highest during the first year of life, decreasing in mid life and increasing again in elderly persons ( Ray et al ., 2007). (E) complications : *Seizures: Persistent , focal or appear late in the course of disease are more likely to be associated with neurological sequelaes (Chavez-Bueno & McCracken, 2005). *Other complications: include subdural effusions and brain abscesses. Subdural effusions are generally asymptomatic and resolve without neurological sequelae (Prasad , Karlupia , 2007 & Nelson , McCracken , 2005).CNS sequelaes include nerve deafness, cortical blindness, hemiparesis, quadriparesis, muscular hypertonia, ataxia, complex seizure disorders, mental motor retardation, learning disabilities, obstructive hydrocephalus, and cerebral atrophy (Nigrovic et al ., 2007). (II) Aspetic meningitis: According to Lee & Davies ,( 2007) AM is an inflammation of the meninges caused mainly by nonbacterial organisms or other disease processes. AM denotes a clinical syndrome with a predominance of lymphocytes in the CSF in absence of bacterial agents in CSF. Also , AM is an acute infection of the central nervous system that occurs most frequently in infants and young children (Berlin, et al.,1993). It could be either viral, fungal , tuberculous meningitis or other causes ( Rorabough et al ;1993). (A) Pathophysiology: Organisms colonize and penetrate the nasopharyngeal or oropharyngeal mucosa , survive and multiply in the blood stream and they invade host immunological mechanisms and spread through the blood-brain barrier. Infection cannot occur until colonization of the host has taken place (usually in the upper respiratory tract).The mechanisms by which circulating viruses penetrate the blood-brain barrier and seed the CSF to cause meningitis are unclear ( CDC ; 2005). In tuberculous meningitis infection begins in the lung and may spread to the meninges by a variety of routes.Blood-borne spread occurs and 25% of patients with miliary TB have TB meningitis by crossing the blood-brain barrier.A proportionof patients may get TB meningitis from rupture of a cortical focus in the brain (Rich focus) and little proportions get it from rupture of a bony focus in the spine. It is rare and unusual for TB of the spine to cause TB meningitis , but isolated cases have been described(Jain et al .,2006). (B) Symptoms and signs: Clinical presentations and courses of AM are markedly variable. Severity of presentations are correlated with prognosis. They usually start by general viral prodroma for several days which is presented by fever, headache, nausea, vomiting , lethargy, myalgia, dysuria and pyuria (Kung., 2007). Specific prodroma in cases of Varicella zoster virus (VZV), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), Measles and Mumps viruses have been reported such as rash, lymphadenopathy, hepatosplenomegaly and parotid enlargement.Common presentation of viral meningitis and encephalitis is encephalopathy with diffuse neurological symptoms and signs including behavioral and personality changes and/or altered mental status, decreased consciousness, generalized seizures, acute confusional or amnesia states but meningismus and headache are less common. Other nonspecific symptoms may include arthralgia, myalgia, sore throat, weakness and lethargy (Moran et al; 2003). Focal signs such as cranial nerve defects, hemiparesis, focal seizures and autonomic dysfunction are encountered. Other signs of viral meningitis include ataxia , dysphagia and hydrophobia have been reported especially in rabies (Lee et al.2006) . The clinical symptoms of AM are characterized by fever (>38◦C), malaise, vomiting and in some cases petechial rashes. Signs of meningeal irritation include neck stiffness,Kernig’s sign and Brudzinski’s sign .These signs are poorly noted in adults . The nonspecific nature of the symptoms and clinical signs mean that we must confirm the diagnosis (Thomas, 2002) . A variety of clinical manifestations which are associated with enteroviral infections , include respiratory illness, acute hemorrhagic conjunctivitis, myocarditis, neonatal sepsis-like disease, encephalitis and acute flaccid paralysis (Jen-Ren et al;2002) . The clinical features of tuberculous meningitis are non-specific , therefore the discrimination of cases of tuberculous meningitis from other causes of meningitis by clinical features alone is often impossible (Thwaites & Tran, 2005). (C) Epidemiology : The epidemiology of AM and other CNS infections are not fixed and may vary according to location and season (Tyler ,2004). Viral meningitis occurs worldwide as epidemics and as sporadic cases. Cases of enteroviral meningitis are observed increased in the late summer (Tyler ,2004). The incidence of tuberculous meningitis(TBM) is related to the prevalence of TB in the community, and it is still the most common type of chronic CNS infection in developing countries. TB is the seventh leading cause of death and disability worldwide ( Dinnes et al ., 2007). (D) Etiology of aseptic meningitis : Many etiological agents are responsible for AM. Viruses are the most frequent causes. 1-Viruses: a-Enterovirus :Enteroviruses(EVs)belong to the family of Picornaviridae. EVs are small, non enveloped, single-stranded RNA viruses that have been classified into 68 serotypes (Stanway et al.,2005) . EVs include polioviruses and non polioviruses which are including echovirus and coxsackievirus(Andreoletti et al. 1998).All the EVs groups are the common etiological agents of AM (Leite & Barbosa , 2005). Enteroviral meningitis is commonly diagnosed in children less than 5 years of age. It is a febrile illness with anorexia and general malaise or may present as a rather abrupt onset of fever, nausea and headache. It could be followed by meningeal signs with stiffness of the neck or back and muscle weakness may occur which is clinically similar to mild poliomyelitis (Yerly et al; 1996). b-Echovirus : Echovirus is RNA virus that belongs to the genus enterovirus(non polio type) of the picornaviridae family. Echovirus is found in the gastrointestinal tract and hence it is being part of the enterovirus genus (Hauri et al ., 2005). Echovirus is highly infectious and its primary target is children. The echovirus is among the leading causes of acute febrile illness in infants and young children ( Chen et al ., 2005). Echovirus causes a nonspecific exanthemas, herpangina which is a fever and skin rashes that may be maculopapular, morbilliform, macular, petechial or papulopustular in nature ( Pichichero et al ., 1998). Severe forms of disease may be complicated by meningitis especially in infants younger than 3 months and encephalitis, neonatal sepsis and myocarditis especially in patients with altered immunity (Paananen et al ., 2003). c-Herpesvirus : Human herpes viruses include herpes simplex virus (HSV) type I (HSVl ) and type 2 (HSV2),VZV,CMV, Human herpesvirus 6 (HHV6) and EBV(Cardone et al., 2007). HSV AM is most commonly associated with primary genital infection with HSV type 2. Acute AM has also been associated with VZV in patients with or without typical skin lesions. Cases of recurrent Mollaret's meningitis have been associated with HSV type 1, HSV type 2 and EBV( Subramanian & Geraghty, 2007). The structure of herpes virus is spherical in shape. Its lipid envelope encloses the nucleocapsid that arranged in a icosahedral form. Its genome is a single, linear, double-stranded molecule. The capsid is surrounded by a number of loosely associated proteins known collectively as the tegument. Many of these proteins play critical roles in initiating the process of virus reproduction in the infected cell. The tegument is in turn covered by a lipid envelope studded with glycoproteins that are displayed on the exterior of the virion (Mettenleiter et al.,2006). The majority of patients with HSV meningitis present with subacute neurological symptoms developing over 1-7 days and the classic symptoms include: headache, neck stiffness, fever, chills, photophobia with other common meningeal symptoms such as vomiting, seizures and altered consciousness. These manifestations are not evident in infants and elderly ( Fatahzadeh &Schwartz,2007) . Figure 1 :Structure of herpesvirs (Roizman et al ., 2006) d-Cytomegalovirus : Cytomegalovirus (CMV) is a viral genus of the herpesviruses group in humans and it is commonly known as human cytomegalovirus (HCMV) or human herpesvirus 5 (HHV-5) (Adler , 2005). All herpesviruses share a characteristic ability to remain latent within the body over long periods and its structure is similar to HSV structure (Bennekov et al ., 2004). HCMV infection may be a life threatening condition especially in immunocompromised patients. Active infection in healthy children and adults can cause prolonged high fever, chills, severe tiredness, a generally ill feeling, headache and spleenomegaly.Most infected newborns have no symptoms at birth but in some cases symptoms include poor weight gain, swollen glands, rash, liver, lung and blood involvement (Bottieau et al .,2006). Patients with impaired immune systems are more prone to serious, potentially life-threatening illnesses, with fever, pneumonia, CNS complications as meningitis , encephalitis ,liver involvement and anaemia. Illnesses can last for weeks or months and can be fatal. In persons with human immunodeficiency virus (HIV) infection , CMV can infect the retina of the eye (CMV retinitis) and cause blindness (Griffiths & Walter , 2005). e-Epstein-Barr virus : EBV or human herpesvirus 4 infects more than 95% of the world's population. The most common manifestation of primary infection with this virus is acute infectious mononucleosis(glandular fever) which is a self-limited clinical syndrome and frequently affects adolescents and young adults (Nicholas & Joseph ,2008). A mature infectious viral particle consists of nucleoid , capsid and an envelope. The nucleoid contains linear double-stranded viral DNA. It is surrounded by icosahedral capsid which is constructed of capsomers which are tubular protein subunits.The envelope derived either from the outer membrane or the nuclear membrane of the host cell encloses the capsid and nucleoid ( the nucleocapsid) (Gasser et al., 2007). Classical symptoms of acute infectious mononucleosis include sore throat, fever, headache and myalgia with generalized lymphadenopathy and splenomegaly , mononucleosis with relative and absolute lymphocytosis. Infection with EBV in younger children is usually asymptomatic or mild. However, EBV is also a human tumor virus which is the first virus associated with human malignancy as nasopharyngeal carcinoma and Burkitt lymphoma (Chaganti et al., 2008). Nonfatal complications are encountered as various forms of CNS and hematological affection.CNS affections are in the form of meningitis, encephalitis, hemiplegia and transverse myelitis. Hematological affection as EBV can cause autoimmune hemolytic anemia and various cytopenias ( Lockey et al., 2008). f-Varicella zoster virus : Varicella zoster virus (VZV) or human herpesvirus 3 is a member of eight herpes viruses known to infect humans. It commonly causes chicken-pox in children and both shingles and postherpetic neuralgia in adults (Steiner et al., 2007). VZV is closely related to the herpes simplex viruses (HSV) sharing much genome homology (CDC,1996). Chicken-pox (varicella) may rarely causes complications as meningitis ,encephalitis or pneumonia. VZV remains dormant in the nervous system of the infected person (virus latency) in the trigeminal and dorsal root ganglia. In about 10-20% of cases, VZV reactivates later in life producing a disease known as herpes zoster or shingles. Serious complications of shingles include postherpetic neuralgia, zoster multiplex, myelitis, AM , herpes ophthalmicus (Steiner et al., 2007). g-Measles virus :Measles is one of the typical viral diseases of childhood. However, unlike other common viral diseases , measles often leads to severe complications that may be fatal ( Helfand et al. ,2008). Measles virus is a member of the family of Paramyxoviruses which is enveloped,single strand RNA(ssRNA)with helical symmetry.The envelop has only one glycoprotein type which is haemaglutinin (HA-antigen) (Leonard et al., 2008). Figure 2:Structure of measles virus (MicrobiologyBytes , 2008). The classical symptoms of measles include a four day fever up to 40°C ,cough, coryza (runny nose) and conjunctivitis (red eyes). Pathognomonic koplik's spots are seen inside the mouth.The characteristic rashs are classically described as a generalized,maculopapular and erythematous that begin several days after the fever starts. They begin on the head before spreading to cover most of the body and often cause itching. The rashs change colour from red to dark brown before disappearing (Perry et al., 2004). Complications with measles are relatively common ranging from relatively mild to sever include diarrhea , pneumonia , encephalitis , meningitis, corneal ulceration leading to corneal scarring (Torjesen ,2008). h-Mumps virus : Mumps or epidemic parotids is a viral disease of the human species. It is a paramyxovirus with the same genetic structure as Measles virus (Hviid et al ., 2008). It manifested by painful swelling of the salivary glands (classically the parotid gland) . Painful testicular swelling and rash may also occur. The symptoms are generally not severe in children. In teenage males and adults, complications such as infertility or subfertility are more common due to orchitis (testicular inflammation).Central complications include AM which is commonly occurring asymptomatically with inflammatory cells in CSF 50%–60% of patients.Symptomatic meningitis (headache, stiff neck) occurs in up to 15% of patients and resolves without sequelae in 3–10 days (Kanra et al ., 2004). The disease is generally self-limited and the symptoms can be controlled by painkillers druges (Preveden et al ., 1996). i-Rubella Virus : Rubella is commonly known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is often mild and attacks often pass unnoticed. The disease can last one to five days. Children recover more quickly than adults. Infection of the mother by Rubella virus during pregnancy is serious especially in the first 20 weeks of pregnancy as the child may be born with congenital rubella syndrome (CRS) (Richardson et al ., 2001). Rubella virus is the only member of the Rubivirus genus of the Togavirus family. Unlike most Togaviruses it is not arthropod-borne but is acquired via the respiratory route. It is an enveloped (toga=cloak), non-segmented, positive sense, RNA virus (Dayan et al., 2006 & Stegmann, Carey , 2002). After an incubation period of 14-21 days, the primary symptom is the appearance of a rash (exanthema) on the face which spreads to the trunk and limbs and usually fades after three days and the rash disappears after a few days with no staining or peeling of the skin. Other symptoms include low grade fever, post cervical lymphadenopathy, joint pain, headache and conjunctivitis. ( Atreya et al., 2004). Rubella can cause congenital rubella syndrome in the newly born. The syndrome (CRS) follows intrauterine infection by the virus and comprises cardiac, cerebral, ophthalmic and auditory defects. It may also cause prematurity, low birth weight , neonatal thrombocytopenia, anaemia and hepatitis (De Santis et al ., 2006 ). In most cases there is neural involvement , irritability, motor tone problems, mental retardation,meningitis, encephalitis , abnormal posture and neurosensory hearing loss ( Weisinger & Pesudovs ,2002). j- Lymphocytic Choriomeningitis virus : Lymphocytic choriomeningitis or lymphocytic meningoencephalitis (LCM) is a rodent-borne viral infectious disease that may cause AM , encephalitis or meningoencephalitis. The causative agent is the lymphocytic choriomeningitis virus (LCMV) which is a member of the family Arenaviridae which is ssRNA , enveloped virus (Barton & Mets , 2001). In humans LCMV infection usually causes mild illness such as fever, fatigue, loss of appetite, muscle aches, headache, nausea and vomiting. A small number of individuals may become quite ill and develop meningitis or encephalitis .Other individuals may not have any symptoms (Barton & Mets , 2001). Figure 3 : Diagram and electron micrograph of LCMV. International Committee on Taxonomy of Viruses database Management( ICTVdB) , 2006.

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