World Journal of Pharmacy and Biotechnology. World Journal of Pharmacy and Biotechnology

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1 B. Kumar et al, WJPBT, 2015, 2(2): ISSN: World Journal of Pharmacy and Biotechnology Journal Home Page: Review Article A Review on Meningitis Open Access Sk. Meharunnisa, B. Kumar*, M. Gobinath Department of Pharmacy Practice, Ratnam India Institute of Pharmacy, Pidathapolur, Muthukur (M), Nellore, Andhra Pradesh, A B S T R A C T Meningitis is an inflammatory disease of meninges membrane that covers the brain and spinal cord. Meningitis is more common in the neonatal period than any other time in life and is an important cause of morbidity and mortality globally. Despite the majority of the burden occurring in the developing world, the majority of the existing literature originates from wealthy countries. Mortality from neonatal meningitis in developing countries is estimated to be 40 58%, against 10% in developed countries. Important differences exist in the spectrum of pathogens isolated from cerebrospinal fluid cultures in developed versus developing countries. Bacterial Meningitis diagnosed by Staining methods. Group B streptococcus (GBS), Escherichia coli and Listeria monocytogenes as important organisms, we describe how in the developing world results have varied; particularly regarding GBS, other Gram negatives (excluding E. coli), Listeria and Gram -positive organisms. The choices of antibiotics are take into consideration of the treatment. Keywords: Meningitis, Brain, spinal cord, antibiotics.etc. A R T I C L E I N F O CONTENTS 1. Introduction Causes Mechanism Diagnosis Prevention Conclusion Reference Article History: Received 15 October 2015, Accepted 28 November 2015, Available Online 29 December 2015 *Corresponding Author B. Kumar Department of Pharmacy Practice, Ratnam Institute of Pharmacy, Pidathapolur, Nellore, Andhra Pradesh, India Manuscript ID: WJPBT2829 PAPER-QR CODE Citation: B. Kumar, et al. A Review on Meningitis. W. J. Pharm. Biotech., 2015, 2(2): Copyright 2015 B. Kumar, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. 1. Introduction Meningitis is a life- threatening infection of the brain, especially on the protective membranes thatt cover the brain World Journal of Pharmacy and Biotechnology and spinal cord. These membranes are known as the meninges. They consist of 3 connective tissue layers which 50

2 are the pia meter, the arachnoid and the dura mater. The brain may be infected by bacteria, fungus or virus, which will cause the inflammation of the meninges. Patients need to receive the treatment within a very short time because it is can be lethal. Meningitis can be classified further into three main groups based on the causative agents --bacterial meningitis, nonbacterial meningitis, and viral meningitis. Bacterial meningitis is usually caused by Pneumococcal species, Haemophilus influenza, Staphylococcal species, and meningococcal species. The bacteria causing meningitis is mainly transmitted through water droplets from person to person. These can be promoted through intimate and prolonged contact, for instance, kissing, sneezing or coughing on another person and staying very close to the infected person. Incidence rate of meningitis in developing countries such as Africa and India is higher than that in the developed countries by ten times since the access to preventive measures of the disease is still not well developed. Every year, there will be 8000 cases of meningitis and a total number of 2000 deaths occur that mark this disease as high morbidity and mortality. Between 1998 and 2003, there is a decline in the cases from 1.9 to 1.5 per 100,000 for the overall incidence of bacterial meningitis. The decrease in the figure was partly contributed by the promoted use of the vaccination especially in many developed countries. In 1986, the median age for persons having infected by bacterial meningitis was 15 months, while in 1998, the median age has been changed to 25 years. This reveals that the disease has a higher frequency in adults than in children even though patients younger than 5 years old are at high risk to get the disease. For the adults, the incidences of bacterial meningitis are 1.7 to 7.2 cases per 100,000 every year and the mean annual incidence is 3.8 cases per 100,000. There are a few common symptoms of meningitis, for instance, neck stiffness, altered mental status, fever and headache. However, the classic triad of fever, neck stiffness and an altered mental status remains low among adults with community- acquired bacterial meningitis. Signs and symptoms: Head ache, High fever, abnormal skin color, Confusion (or) altered consciousness, Photophobia, Nuchal rigidity and Photophobia. 2. Causes consciousness if inflammation and damage to the brain cannot be successfully stopped with antibiotics and other treatments, the infection can be fatal. Usually the most common bacteria that cause meningitis are Streptococcus pneumonie and Neisseria meningitides. Streptococcus pneumonia usually causes pneumococcal meningitis. There are over 80 subtypes that cause the illness. Streptococcus pneumonia can be found in the throat and usually people don t get sick from them. The people who are at risk getting pneumococcal meningitis or pneumonia are those with weak immune systems or people who are very young and very old. People who get direct contact with someone who have pneumonia meningitis do not have to take antibiotics. Meningococcal is a fast moving disease and can cause death in 24 to 48 hours starting from the start of the symptoms. It can cause two types of infection, meningococcal meningitis which cause meninges and the other one is meningoccemia or known as septicemia. Septicaemia is blood poisoning caused by bacteria in the bloodstream. Virus: Virus the first few signs of infection by viral and bacterial meningitis are both characterised by rapid onset of fever, headache, nausea and throwing up. Therefore, it is rather difficult to diagnose whether the acute meningitis is caused by bacteria or viruses. Usually, evaluations will be made to determine presence for other symptoms like possible encephalitis, seizures, reduced Glasgow coma score, or focal neurological signs. For bacterial infection cases, patients who are left untreated will display retardation of mental status while virally infected meningitis patients will recover on their own after some time. The most common agents that cause viral meningitis are Enteroviruses. Infections by these viruses are mainly without symptoms, but they cause systemic infections and may attack the brain neurons and cause aseptic meningitis, meningocephalitis and paralytic poliomyelitis. Sudden retardation in mental status or occurrence seizures may be due to the progression from meningitis to meningocephalitis. It may also have other accompanied signs such as herpangina; hand-foot-mouth disease and generalised maculopapular rash. Enteroviruses include Coxsackie A and B viruses, echoviruses, polioviruses, Human immunodeficiency virus and Epstein Barr Virus. Newborns and toddlers whose immune system is not completely developed will be very vulnerable to infections by enteroviruses Herpes simplex virus is another causative agent of meningitis. It is actually a complication from a primary genital herpes infection. Non-primary genital herpes infection seldom leads to the incidence of meningitis. The viral meningitis caused by herpes simplex virus might recur and lead to a relapse. Bacteria: When bacteria invade the cerebrospinal fluid (CSF), the bacteria can multiply freely in CSF, and there they release poisons, causing inflammation and swelling in the meninges and the brain tissue itself. This will increase the pressure inside the brain, producing symptoms of meningitis such as headache, stiff neck and dislike of bright lights. Babies become irritable, may have a high-pitched or 3. Mechanism moaning cry, be stiff or floppy, and develop a bulging soft The meninges comprise three membranes that, together with spot on their head. In both children and adult, there may be the cerebrospinal fluid, enclose and protect a rash, which can occur all anywhere on the body. This is a the brain and spinal cord (the central nervous system). sign of blood poisoning (septicemia) which sometimes The pia mater is a very delicate impermeable membrane that happens because of meningococcal strains. As the disease firmly adheres to the surface of the brain, following all the progresses the patient becomes drowsy, confused, and minor contours. The arachnoid mater (so named because of delirious. They may have seizures and eventually lose its spider-web-like appearance) is a loosely fitting sac on top World Journal of Pharmacy and Biotechnology 51

3 of the pia mater. The subarachnoid space separates the arachnoid and pia mater membranes and is filled with cerebrospinal fluid. The outermost membrane, the dura mater, is a thick durable membrane, which is attached to both the arachnoid membrane and the skull. In bacterial meningitis, bacteria reach the meninges by one of two main routes: through the bloodstream or through direct contact between the meninges and either the nasal cavity or the skin. In most cases, meningitis follows invasion of the bloodstream by organisms that live upon mucous surfaces such as the nasal cavity. This is often in turn preceded by viral infections, which break down the normal barrier provided by the mucous surfaces. Once bacteria have entered the bloodstream, they enter the subarachnoid space in places where the blood brain barrier is vulnerable such as the choroid plexus. Meningitis occurs in 25% of newborns with bloodstream infections due to group B streptococci; this phenomenon is less common in adults. Direct contamination of the cerebrospinal fluid may arise from indwelling devices, skull fractures, or infections of the nasopharynx or the nasal sinuses that have formed a tract with the subarachnoid space (see above); occasionally, congenital defects of the Dura can be identified. The large-scale inflammation that occurs in the subarachnoid space during meningitis is not a direct result of bacterial infection but can rather largely be attributed to the response of the immune system to the entry of bacteria into the central nervous system. When components of the bacterial cell membrane are identified by the immune cells of the brain (astrocytes and microglia), they respond by releasing large amounts of cytokines, hormone-like mediators that recruit other immune cells and stimulate other tissues to participate in an immune response. The blood brain barrier becomes more permeable, leading to "vasogenic" cerebral edema (swelling of the brain due to fluid leakage from blood vessels). Large numbers of white blood cells enter the CSF, causing inflammation of the meninges and leading to "interstitial" edema (swelling due to fluid between the cells). In addition, the walls of the blood vessels themselves become inflamed (cerebral vasculitis), which leads to decreased blood flow and a third type of edema, "cytotoxic" edema. The three forms of cerebral edema all lead to increased intracranial pressure; together with the lowered blood pressure often encountered in acute infection, this means that it is harder for blood to enter the brain; consequently brain cells are deprived of oxygen and undergo apoptosis (automated cell death). 4. Diagnosis: Blood tests and imaging: Lumbar puncture: Gram stain of meningococci from a culture showing Gram negative (pink) bacteria, often in pairs. 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 18 cm water (cmh 2 O); 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 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. Postmortem: Histopathology of bacterial meningitis: autopsy case of a person with pneumococcal meningitis showing inflammatory infiltrates of the mate consisting of neutrophil granulocytes (inset, higher magnification). 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. 5. Prevention: For some causes of meningitis, protection can be provided in the long term through vaccination, or in the short term with antibiotics. Some behavioral measures may also be effective. Behavioral Bacterial and viral meningitis are contagious; however, neither is as contagious as the common cold or flu. Both can be transmitted through droplets of respiratory secretions during close contact such as kissing, sneezing or coughing on someone, but cannot be spread by only breathing the air where a person with meningitis has been. Viral meningitis is typically caused by enteroviruses, and is most commonly spread through fecal contamination. The risk of infection can be decreased by changing the behavior that led to transmission. Vaccination: Since the 1980s, many countries have included immunization against Haemophilus influenzae type B in their routine childhood vaccination schemes. This has practically eliminated this pathogen as a cause of meningitis in young using a manometer. The pressure is normally between 6 and children in those countries. World Journal of Pharmacy and Biotechnology 52

4 Meningococcus vaccines exist against groups A, B, C, W135 and Y. In countries where the vaccine for meningococcus group C was introduced, cases caused by this pathogen have decreased substantially. Routine vaccination against Streptococcus pneumonia with the pneumococcal conjugate vaccine (PCV), which is active against seven common serotypes of this pathogen, significantly reduces the incidence of pneumococcal meningitis. Childhood vaccination with Bacillus Calmette-Guérin has been reported to significantly reduce the rate of tuberculosis meningitis, but its waning effectiveness in adulthood has prompted a search for a better vaccine. Antibiotics: Short-term antibiotic prophylaxis is another method of prevention, particularly of meningococcal meningitis. In cases of meningococcal meningitis, prophylactic treatment of close contacts with antibiotics can reduce their risk of contracting the condition, but does not protect against future infections. Resistance to rifampicin has been noted to increase after use, which has caused some to recommend considering other agents. While antibiotics are frequently used in an attempt to prevent meningitis in those with a basilar skull fracture there is insufficient evidence to determine whether this is beneficial or harmful. This applies to those with or without a CSF leak. Management: Bacterial meningitis: Antibiotics: Empiric antibiotics (treatment without exact diagnosis) should be started immediately, even before the results of the lumbar puncture and CSF analysis are known. The choice of initial treatment depends largely on the kind of bacteria that cause meningitis in a particular place and population. For instance, in the United Kingdom empirical treatment consists of a third-generation cephalosporin such as cefotaxime or ceftriaxone. In the USA, where resistance to cephalosporins is increasingly found in streptococci, addition of vancomycin to the initial treatment is recommended. Chloramphenicol, either alone or in confined to those with pneumococcal meningitis, some guidelines suggest that dexamethasone be discontinued if another cause for meningitis is identified. The likely mechanism is suppression of overactive inflammation. Viral meningitis: Viral meningitis typically only requires supportive therapy; most viruses responsible for causing meningitis are not amenable to specific treatment. Viral meningitis tends to run a more benign course than bacterial meningitis. Herpes simplex virus and varicella zoster virus may respond to treatment with antiviral drugs such as acyclovir, but there are no clinical trials that have specifically addressed whether this treatment is effective. Fungal meningitis: Fungal meningitis, such as cryptococcal meningitis, is treated with long courses of high dose antifungal, such as amphotericin-b and flu cytosine. Raised intracranial pressure is common in fungal meningitis, and frequent (ideally daily) lumbar punctures to relieve the pressure are recommended, or alternatively a lumbar drain. Prognosis: Untreated, bacterial meningitis is almost always fatal. Viral meningitis, in contrast, tends to resolve spontaneously and is rarely fatal. With treatment mortality (risk of death) from bacterial meningitis depends on the age of the person and the underlying cause. Of newborns, 20 30% may die from an episode of bacterial meningitis. This risk is much lower in older children, whose mortality is about 2%, but rises again to about 19 37% in adults. Risk of death is predicted by various factors apart from age, such as the pathogen and the time it takes for the pathogen to be cleared from the cerebrospinal fluid, the severity of the generalized illness, a decreased level of consciousness or an abnormally low count of white blood cells in the CSF. Meningitis caused by H. influenza and meningococci has a better prognosis than cases caused by group B streptococci, coli forms and S. pneumonia. In adults, too, meningococcal meningitis has a lower mortality (3 7%) than pneumococcal disease. In children there are several potential disabilities which may result from damage to the nervous system, including sensor neural, epilepsy, learning, and behavioral difficulties, as well as decreased intelligence. These occur in about 15% of survivors. Some of the hearing loss may be reversible. In adults, 66% of all cases emerge without disability. The main problems are deafness (in 14%) and cognitive (in 10%). Tuberculosis meningitis in children continues to be associated with a significant risk of death even with treatment (19%), and a significant proportion of the surviving children have ongoing neurological problems. Just over a third of all cases survive with no problems. combination with ampicillin, however, appears to work equally well. Empirical therapy may be chosen on the basis of the person's age, whether the infection was preceded by a head injury, whether the person has undergone recent neurosurgery and whether or not a cerebral shunt is present. In young children and those over 50 years of age, as well as those who are immunocompromised, the addition of ampicillin is recommended to cover Listeria monocytogenes. Steroids: Adjuvant treatment with corticosteroids (usually dexamethasone) has shown some benefits, such as a reduction of hearing loss and better short term neurological outcomes in adolescents and adults 6. Conclusion from high-income countries with low rates of HIV. Some Chronic meningitis is an inflammation of the meninges that research has found reduced rates of death while other lasts for more than 4 weeks. It has infectious (bacterial, research has not. They also appear to be beneficial in those viral, fungal, and parasitic) and noninfectious sources with tuberculosis meningitis, at least in those who are HIV (granulomatous and inflammatory diseases, drugs, and negative. Professional guidelines therefore recommend the neoplasm). CSF findings are nonspecific, but usually well commencement of dexamethasone or a similar corticosteroid defined for each cause. Treatment of infectious sources just before the first dose of antibiotics is given, and continued usually involves antimicrobials. Mortality is often high but for four days. Given that most of the benefit of the treatment is can be prevented with appropriate medical therapy. World Journal of Pharmacy and Biotechnology 53

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