Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT03759470 |
| Other study ID # |
Doha Fahmy |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2019 |
| Est. completion date |
December 31, 2019 |
Study information
| Verified date |
November 2018 |
| Source |
Assiut University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Bacterial meningitis occurs in about 3 people per 100,000 annually in Western countries. .
Description:
meningitis is a notifiable disease in many countries, the exact incidence rate is unknown. In
2013 meningitis resulted in 303,000 deaths - down from 464,000 deaths in 1990. In 2010 it was
estimated that meningitis resulted in 420,000 deaths, excluding cryptococcal meningitis.
Bacterial meningitis occurs in about 3 people per 100,000 annually in Western countries.
Population-wide studies have shown that viral meningitis is more common, at 10.9 per 100,000,
and occurs more often in the summer. In Brazil, the rate of bacterial meningitis is higher,
at 45.8 per 100,000 annually.Sub-Saharan Africa has been plagued by large epidemics of
meningococcal meningitis for over a century,leading to it being labeled the "meningitis
belt". Epidemics typically occur in the dry season (December to June), and an epidemic wave
can last two to three years, dying out during the intervening rainy seasons.Attack rates of
100-800 cases per 100,000 are encountered in this area, which is poorly served by medical
care. These cases are predominantly caused by meningococci.The largest epidemic ever recorded
in history swept across the entire region in 1996-1997, causing over 250,000 cases and 25,000
deaths.
Meningococcal disease occurs in epidemics in areas where many people live together for the
first time, such as army barracks during mobilization, college campuses and the annual Hajj
pilgrimage. Although the pattern of epidemic cycles in Africa is not well understood, several
factors have been associated with the development of epidemics in the meningitis belt. They
include: medical conditions (immunological susceptibility of the population), demographic
conditions (travel and large population displacements), socioeconomic conditions
(overcrowding and poor living conditions), climatic conditions (drought and dust storms), and
concurrent infections (acute respiratory infections).
There are significant differences in the local distribution of causes for bacterial
meningitis. For instance, while N. meningitides groups B and C cause most disease episodes in
Europe, group A is found in Asia and continues to predominate in Africa, where it causes most
of the major epidemics in the meningitis belt, accounting for about 80% to 85% of documented
meningococcal meningitis cases.
Infections that involve the central nervous system (CNS), such as meningitis/encephalitis
(ME), are severe clinical conditions associated with high rates of morbidity and mortality as
well as significant long-term sequelae . acute inflammation of the protective membranes
covering the brain and spinal cord, known collectively as the meninges.The most common
symptoms are fever, headache, and neck stiffness.Other symptoms include confusion or altered
consciousness, vomiting, and an inability to tolerate light or loud noises. Young children
often exhibit only nonspecific symptoms, such as irritability, drowsiness, or poor feeding.If
a rash is present, it may indicate a particular cause of meningitis; for instance, meningitis
caused by meningococcal bacteria may be accompanied by a characteristic rash. The
inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and
less commonly by certain drugs.Meningitis can be life-threatening because of the
inflammation's proximity to the brain and spinal cord; therefore, the condition is classified
as a medical emergency. A lumbar puncture can diagnose or exclude meningitis.A needle is
inserted into the spinal canal to collect a sample of cerebrospinal fluid (CSF), which
envelops the brain and spinal cord. The CSF is examined in a medical laboratory.
Some forms of meningitis are preventable by immunization with the meningococcal, mumps,
pneumococcal, and Hib vaccines.Giving antibiotics to people with significant exposure to
certain types of meningitis may also be useful.The first treatment in acute meningitis
consists of promptly giving antibiotics and sometimes antiviral drugs.Corticosteroids can
also be used to prevent complications from excessive inflammation. Meningitis can lead to
serious long-term consequences such as deafness, epilepsy, hydrocephalus, or cognitive
deficits, especially if not treated quickly.
most common symptom of meningitis is a severe headache, occurring in almost 90% of cases of
bacterial meningitis, followed by nuchal rigidity (the inability to flex the neck forward
passively due to increased neck muscle tone and stiffness). The classic triad of diagnostic
signs consists of nuchal rigidity, sudden high fever, and altered mental status; however, all
three features are present in only 44-46% of bacterial meningitis cases.If none of the three
signs are present, acute meningitis is extremely unlikely.Other signs commonly associated
with meningitis include photophobia (intolerance to bright light) and phonophobia
(intolerance to loud noises). Small children often do not exhibit the aforementioned
symptoms, and may only be irritable and look unwell.The fontanelle (the soft spot on the top
of a baby's head) can bulge in infants aged up to 6 months. Other features that distinguish
meningitis from less severe illnesses in young children are leg pain, cold extremities, and
an abnormal skin color.
Nuchal rigidity occurs in 70% of bacterial meningitis in adults. Other signs include the
presence of positive Kernig's sign or Brudziński sign. Kernig's sign is assessed with the
person lying supine, with the hip and knee flexed to 90 degrees. In a person with a positive
Kernig's sign, pain limits passive extension of the knee. A positive Brudzinski's sign occurs
when flexion of the neck causes involuntary flexion of the knee and hip. Although Kernig's
sign and Brudzinski's sign are both commonly used to screen for meningitis, the sensitivity
of these tests is limited.They do, however, have very good specificity for meningitis: the
signs rarely occur in other diseases. Another test, known as the "jolt accentuation maneuver"
helps determine whether meningitis is present in those reporting fever and headache. A person
is asked to rapidly rotate the head horizontally; if this does not make the headache worse,
meningitis is unlikely.
Other problems can produce symptoms similar to those above, but from non-meningitic causes.
This is called meningism or pseudomeningitis.
Meningitis caused by the bacterium Neisseria meningitidis (known as "meningococcal
meningitis") can be differentiated from meningitis with other causes by a rapidly spreading
petechial rash, which may precede other symptoms.The rash consists of numerous small,
irregular purple or red spots ("petechiae") on the trunk, lower extremities, mucous
membranes, conjuctiva, and (occasionally) the palms of the hands or soles of the feet. The
rash is typically non-blanching; the redness does not disappear when pressed with a finger or
a glass tumbler. Although this rash is not necessarily present in meningococcal meningitis,
it is relatively specific for the disease; it does, however, occasionally occur in meningitis
due to other bacteria. Other clues on the cause of meningitis may be the skin signs of hand,
foot and mouth disease and genital herpes, both of which are associated with various forms of
viral meningitis.
Additional problems may occur in the early stage of the illness. These may require specific
treatment, and sometimes indicate severe illness or worse prognosis. The infection may
trigger sepsis, a systemic inflammatory response syndrome of falling blood pressure, fast
heart rate, high or abnormally low temperature, and rapid breathing. Very low blood pressure
may occur at an early stage, especially but not exclusively in meningococcal meningitis; this
may lead to insufficient blood supply to other organs.Disseminated intravascular coagulation,
the excessive activation of blood clotting, may obstruct blood flow to organs and
paradoxically increase the bleeding risk. Gangrene of limbs can occur in meningococcal
disease.Severe meningococcal and pneumococcal infections may result in hemorrhaging of the
adrenal glands, leading to Waterhouse-Friderichsen syndrome, which is often fatal.
The brain tissue may swell, pressure inside the skull may increase and the swollen brain may
herniate through the skull base. This may be noticed by a decreasing level of consciousness,
loss of the pupillary light reflex, and abnormal posturing.The inflammation of the brain
tissue may also obstruct the normal flow of CSF around the brain (hydrocephalus).Seizures may
occur for various reasons; in children, seizures are common in the early stages of meningitis
(in 30% of cases) and do not necessarily indicate an underlying cause.Seizures may result
from increased pressure and from areas of inflammation in the brain tissue. Focal seizures
(seizures that involve one limb or part of the body), persistent seizures, late-onset
seizures and those that are difficult to control with medication indicate a poorer long-term
outcome.
Inflammation of the meninges may lead to abnormalities of the cranial nerves, a group of
nerves arising from the brain stem that supply the head and neck area and which control,
among other functions, eye movement, facial muscles, and hearing. Visual symptoms and hearing
loss may persist after an episode of meningitis.Inflammation of the brain (encephalitis) or
its blood vessels (cerebral vasculitis), as well as the formation of blood clots in the veins
(cerebral venous thrombosis), may all lead to weakness, loss of sensation, or abnormal
movement or function of the part of the body supplied by the affected area of the brain.
Meningitis is typically caused by an infection with microorganisms. Most infections are due
to viruses,with bacteria, fungi, and protozoa being the next most common causes. It may also
result from various non-infectious causes. The term aseptic meningitis refers to cases of
meningitis in which no bacterial infection can be demonstrated. This type of meningitis is
usually caused by viruses but it may be due to bacterial infection that has already been
partially treated, when bacteria disappear from the meninges, or pathogens infect a space
adjacent to the meninges (e.g. sinusitis). Endocarditis (an infection of the heart valves
which spreads small clusters of bacteria through the bloodstream) may cause aseptic
meningitis. Aseptic meningitis may also result from infection with spirochetes, a group of
bacteria that includes Treponema pallidum (the cause of syphilis) and Borrelia burgdorferi
(known for causing Lyme disease). Meningitis may be encountered in cerebral malaria (malaria
infecting the brain) or amoebic meningitis, meningitis due to infection with amoebae such as
Naegleria fowleri, contracted from freshwater sources.
In premature babies and newborns up to three months old, common causes are group B
streptococci (subtypes III which normally inhabit the vagina and are mainly a cause during
the first week of life) and bacteria that normally inhabit the digestive tract such as
Escherichia coli (carrying the K1 antigen). Listeria monocytogenes (serotype IVb) is
transmitted by the mother before birth and may cause meningitis in the newborn.
Older children are more commonly affected by Neisseria meningitidis (meningococcus) and
Streptococcus pneumoniae (serotypes 6, 9, 14, 18 and 23) and those under five by Haemophilus
influenzae type B (in countries that do not offer vaccination).
Tuberculous meningitis, which is meningitis caused by Mycobacterium tuberculosis, is more
common in people from countries in which tuberculosis is endemic, but is also encountered in
persons with immune problems, such as AIDS.
Recurrent bacterial meningitis may be caused by persisting anatomical defects, either
congenital or acquired, or by disorders of the immune system.Anatomical defects allow
continuity between the external environment and the nervous system. The most common cause of
recurrent meningitis is a skull fracture, particularly fractures that affect the base of the
skull or extend towards the sinuses and petrous pyramids. Approximately 59% of recurrent
meningitis cases are due to such anatomical abnormalities, 36% are due to immune deficiencies
(such as complement deficiency, which predisposes especially to recurrent meningococcal
meningitis), and 5% are due to ongoing infections in areas adjacent to the meninges.
Viruses that cause meningitis include enteroviruses, herpes simplex virus (generally type 2,
which produces most genital sores; less commonly type 1), varicella zoster virus (known for
causing chickenpox and shingles), mumps virus, HIV, and LCMV.[20] Mollaret's meningitis is a
chronic recurrent form of herpes meningitis; it is thought to be caused by herpes simplex
virus type 2.
There are a number of risk factors for fungal meningitis, including the use of
immunosuppressants (such as after organ transplantation), HIV/AIDS, and the loss of immunity
associated with aging.It is uncommon in those with a normal immune system but has occurred
with medication contamination.Symptom onset is typically more gradual, with headaches and
fever being present for at least a couple of weeks before diagnosis.The most common fungal
meningitis is cryptococcal meningitis due to Cryptococcus neoformans. In Africa, cryptococcal
meningitis is now the most common cause of meningitis in multiple studies,and it accounts for
20-25% of AIDS-related deaths in Africa.Other less common fungal pathogens which can cause
meningitis include: Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis,
and Candida species.
A parasitic cause is often assumed when there is a predominance of eosinophils (a type of
white blood cell) in the CSF. The most common parasites implicated are Angiostrongylus
cantonensis, Gnathostoma spinigerum, Schistosoma, as well as the conditions cysticercosis,
toxocariasis, baylisascariasis, paragonimiasis, and a number of rarer infections and
noninfective conditions.
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. influenzae and meningococci has a better
prognosis than cases caused by group B streptococci, coliforms 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 sensorineural hearing loss, 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 impairment (in 10%).
Tuberculous 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 survives with no problems.
