Abstract
Infections in the CNS in a normal healthy individual are curbed by the blood-brain barrier which prevents entry of the pathogens and the inflammatory cytokines. Infections can gain access to the CNS by hematological seeding. The etiological agents include bacteria, viruses, parasites, and fungi. TB of the CNS commonly affects the immunocompromised. These include patients undergoing chemotherapy, HIV/AIDS patients, organ donors and organ recipients who are immunosuppressants. TB of the CNS may manifest as meningitis, tuberculomas or abscess. Diagnosis can be done in the lab and through imaging also. In the lab, the CSF is observed macroscopically for any turbidity; biochemistry studies are done, cell differential studies are done to help in determining the causative agent; microscopy, culture, and sensitivity can also be done. Imaging- MRI and CT Scans can also be done. For tuberculomas, there will be a ring surrounding the lesion with edema around the area. Diagnosis and treatment are usually initiated late. This study aims at curbing this by several ways. These include the use of steroids, for example, dexamethasone to control the inflammation of the meninges. Regular chest X-Rays especially to the patients with pulmonary TB, routine GeneXpert studies on the CSF to assess dissemination of the disease to the CNS. GeneXpert will also aid in the determination of resistance to rifampicin and isoniazid. Other treatment modalities will also be employed. This by use of fluoroquinolones and high dose rifampicin. Vaccination of BCG to such patients will also help boost their immunity. Health education to the patients as well their family members will aid in ensuring adherence to the medication is done. This will alleviate the risk of developing resistance to the drugs (Bautista, & Foster, 2013). The TB is spread all the word want to prevelance how much patient have meningitis of TB what cause to inter of mycobacterium to reattach the CNS if he had exposure to any kind of TB before or he had contacte with people how had TB . We want the resarch quantitative retrospective divide team to centers of TB to research for medical records after we get a proved how many patients have developed TB meningitis and why .check the treatment and we will do the prevelance on it for this important there’s no prevelance before and we should awareness the people for the dangerous of TB to reduce the spread. You can inter to WHO to see the incidents of Tb around the world. This is a quantitative retrospictive study of patients (both male and female) at the TB centers, and hospitals in the country and who have and had CNS infection and respiratory symptoms in the past five years. A sample size of depends ontha medical records will be used. The sampling technique will be review the history of patients. Data processing and analyzing methods used will be SPSS and Microsoft Excel will used in the analysis and data processing. (Symon & Cassell, 2012).
Background
Infections in the Central Nervous System (CNS) have a good prognosis if detected early enough- accompanied by appropriate investigations and timely treatment.(Bautista, & Foster, 2013). As this helps in preventing the occurrence of fatal complications(Ritter et al ,2014). put that in a normal healthy individual, there is the blood-brain barrier which prevents the entry of pathogens and inflammatory cells which might affect the integrity of the brain matter (Bautista, & Foster, 2013). put that seeding of infections into the brain is through the hematogenous route or localized infections involving the middle ear cavity or the olfactory nerve. Other ways of which infections are seeded in the CNS is iatrogenically for example during insertion of the ventriculoperitoneal shunt in patients with hydrocephalus or medication which compromised the patients' immunity status for example chemotherapy, use of steroids; illnesses like diabetes mellitus, HIV/AIDs. Various organisms are implicated in the CNS infections(Goodman et al ,2011). put that various factors play a key role in the type of infection that will affect the patient. This includes the patient's immune status, age, epidemiological trends, and existing comorbidities.
Meningitis is caused by bacteria, viruses, fungi, parasites, and drugs, for example, metronidazole, and steroids. In adults, the primary causative agent is Gram-negative bacilli (Haemophilus influenza, Neisseria meningitides, and Streptococcus pneumonia) but the commonest is the pneumococcal organism while in infants and neonates the most prevalent organism is Haemophilus influenza. Other agents include fungal and protozoal agents. Virulence factors of the organisms aid in the colonization of the host. Inflammatory cytokines are released as a way of fighting off the infections. The cytokines affect the barrier allowing proteins and other inflammatory mediators to enter the brain. This then leads to cerebral edema, irritation of the meninges which then causes meningism.
Various investigation modalities can be used to diagnose meningitis. A full hemogram will show a neutrophilic leukocytosis in TB and pyogenic meningitis (Goodman et al, 2011). put that the Erythrocyte Sedimentation Reaction (ESR) and C – reactive protein may be markedly elevated. Microbiology of the blood may reveal the causative organisms. It is about 50% of all the patients. In patients with TB-like symptoms, it is essential to do a chest X-Ray. Cerebrospinal fluid drawn by lumbar puncture can be done different test biochemistry, culture, and macroscopic studies. Imaging modalities include MRI and CT Scans. In HIV/AIDs positive patients, the dominant causative organism is Mycobacterium tuberculosis.
TB of the CNS has a high prevalence and incidence among those with immunosuppression- for example, HIV/AIDS patients, those on chemotherapy, those using steroids among others. Shih et al. (2015) put that TB of the spine can manifest as tuberculoma, abscess or meningitis. They also put that it is associated with a high morbidity and mortality rate worldwide. Even though they get treatment, they are associated with adverse neurological sequelae. The patient presents typically with seizures, photophobia, papilledema and focal neurologic deficits. The infection can spread to the layers of the meninges. Iqbal et al. (2015) put that the lesions may be multiple or solitary and they are usually surrounded by a ring enhancement and edema. They also found out that in children it's typically infratentorial while in adults, it is supratentorial.
The tuberculoma is typically a caseation with typical evidence shown on an MRI and CT scan as evidenced by Skoura et al. (2015). Early treatment is critical in preventing or reducing the risk of neurological sequelae that ensue.
SPECIFICS AIMS
• To identify the prevalence of patient men and women with Central Nervous System that had infected by Mycobacterium Tuberculosis
• To identify the prevalence of CNS Tuberculosis.
• To outline the correlation of the CNS tuberculum’s and TB patients.
This study aims to update the available data on the magnitude of CNS tuberculosis. It is also the aim of the study to change public health attitude toward tuberculosis. The broad objective of the study is to determine the prevalence and incidence of tuberculosis infection in the population. The specific objective will be to determine prevalence and incidence of CNS tuberculosis among those infected with Tuberculosis. The study will also aim to compare the difference in prevalence and incidence among different subsets of the population including difference between male and female. The study will also aim to determine the different factors affecting the prevalence of CNS tuberculosis is a population. The study will also aim to determine the spectrum of central nervous system tuberculosis disease. Specifically this will include the prevalence of TB myelopathy, TB spinal vasculopathy, TB meningitis and tuberculoma. The other objective will to determine the mortality and morbidity patterns of CNS tuberculosis. The secondary objectives will to determine the rate of tuberculosis treatment uptake and completion.
SIGNIFICANCE
Tuberculosis of the CNS has dire complications. Some of them include hydrocephalus, neurological deficits for example hemiplegia, hemiparesis, seizures; blindness, deafness, altered mental status among others. Timely diagnosis and correct treatment as well as follow up help in reducing the risk of development of complications and improve the quality of life of these patients. There is paucity of literature reporting on the magnitude of Central Nervous System tuberculosis. Data that is available is largely old. Therefore the prevalence of CNS tuberculosis is largely unknown. The disease is general a problem in sub Saharan Africa and the rest of the developing world has largely been neglected in the developed world. Though the estimate burden of CNS tuberculosis is small, it still affects a significant part of the population, the HIV infected and therefore more attention should be given so as not to leave a part of population neglected. The information will be critical for the part of the population that is affected by TB. The information will be useful in predicting and guiding public health measures. The study will determine the need to initiate isoniazid to specific parts of the population.
INNOVATION
Tuberculosis results in the inflammation of the meninges. The diagnosis of the CNS tuberculosis is usually delayed as well initiation of the treatment. This results in severe complications which can be curbed with early diagnosis. This research aims at ensuring diagnosis is timely and also aims at the initiation of use of steroids dexamethasone which will help in reducing the inflammation of the meninges. Ways of follow up of the patients would be constant monitoring of the CSF by use of GeneXpert studies to look out for any dissemination to the CNS. Regular chest X-Rays will also be used to monitor response to medication especially in patients who have pulmonary TB. This will be one of the ways to help in monitoring response to drugs. The use of BCG vaccination will also be utilized to assist in boosting the patient's immunity.
Another way that will be utilized in treatment includes intrathecal delivery of the drug. This is has been evidenced by Mai et al. (2017) to be effective. Family health education is also paramount in that the patients will be kept in check in the use of their medication which help reduce the risk of resistance to the antibiotics used. Use of biomarkers will also be employed to enhance the diagnosis of the disease, for example, lactate which indicates anaerobic metabolism taking place in the CSF. Zumla et al. (2015) suggest that use of fluoroquinolones and a high dose of rifampicin is being studied which will eventually improve the outcome. Several studies have been done to prove the importance of PCR assays. Takahashi et al. (2012) put that this one of the ways that will help investigate drug resistance patterns in the treatment of CNS tuberculosis. There are studies that support the introduction of PCR based assays to help in the detection of rifampicin resistance in the clinical specimen (Ritter, 2014).
APPROACH
Study Population and sample size determination:
This is a quantitative retrospective study of patients the study included, all adult (age ≥ 18 years) enrolled in the five hospitals of study. will see the medical recored for Patients (both male and female) at the TB centers, and hospitals in the country and who had CNS and respiratory symptoms in the past five years.
The sample size is already predetermined since it is retrospective study and it will involve more than 100 subject. Data will be obtained mainly from medical records in TB centers and hospital identified to ascertain the percentage of patient with TB presenting with CNS disease symptoms.
Study Design and Methods
A retrospective cross-sectional study design will be used. The clients’ records will be retrieved from the hospital registries and research center from the period of 1st January 2014 to 31st December 2017. Client selection will be from the Hospital electronic registry. From the register clients enrolled during the period, will be identified and their files obtained from the archives for the collection of information relevant to the study. Hospital records and patients' files, charts,
radiology reports- MRI and CT scans and laboratory records will be used. The information will include age, sex, HIV status and antiretroviral treatment. Other comorbidities, tuberculosis disease and mortality (Ritter, 2014).
Inclusion Criteria: Case definition:
All patients admitted with tuberculosis infection in in the past five years.
Participants
We will not have active participants as the data will be retrieved from clinic registries and those records who will meet the inclusion criteria will form our participants
Timelines
Activities December-2018 January-February2017 March-2017 April-2017
Proposal writing x
Proposal submission x
Data collection x X
Data analysis X
Manuscript preparation. x
Timeline:
BUDGET
Number Item Cost
1. Printing papers 100$
2. Printing charges 150$
3. Ball point pens 100$
4. Notebooks 200$
5. Stapler and staple pins 100$
6 Transport (to and from the medical centers and hospital) 500$
7. Accommodation charges 150$
Due to lack of funding and inability to get research grants, most researchers are unable to achieve their objectives fully. They are limited by factors like lack of transport, lack of accommodation in the potential study area and lack of enough printing papers to print the questionnaires. Symone et al. (2012) put that with adequate funding and resources, researchers will adequately achieve their objectives.
Assurances
1. The researcher will obtain approval from the Hospitals Ethics and Review committees.
2. There will be no active human participants and thus will be impractical to administer consent to patients whose records will be used, however data collected will not include identifying characteristics such as patient name or inpatient numbers (Symon & Cassell, 2012).
HUMAN SUBJECTS:
The study will involve patient who have had symptoms of CNS disease suggestive of tuberculous meningitis. The subjects under study will be human subjects and they will handled with the greatest care with no harm intended on the subject, No invasive procedures will be subjected to the patients and written consent will be sought for them to be involved in the study. For this type of research, we have to get approve from Institutional Review Boards (IRBs) and starte the process for it. Approval will be communicated via email about a week or two from when they are submitted. All modifications should be reported back to the board. Since human subjects are being used, any cases of subjects complaints and withdrawal from the study. Once all the correction has been done, no further reviewing of the work is indicated. The report can be compiled thereafter. Task forces and subcommittees Formed by the IRB chair, HRPO, and IRB Committee to assist in addressing various scientific issues that have a relationship to the use of human subjects in human subjects’ protection and research. The office of the Human Research Protection oversees IRB. National Commission also protects the human subjects of ethics and Biomedical research for Protection of Human Subjects.