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Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia
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Does CD4 Cell Count Influence CT features of Intracranial Opportunistic Infections in adult HIV/AIDS Patients- EduPublish-MMA Kareem, USM, KB, Malaysia

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The number of HIV cases in Malaysia in people aged 15 to 49 are 80,000 with its current rate of doubling every three years. In Malaysia, opportunistic infections such as Cryptococcus are found to be …

The number of HIV cases in Malaysia in people aged 15 to 49 are 80,000 with its current rate of doubling every three years. In Malaysia, opportunistic infections such as Cryptococcus are found to be associated with advanced HIV infection. In predicting this, a useful guide is by monitoring the CD4 + T-Lymphocyte count. Neuroimaging plays a crucial role in establishing early intracranial involvement. In malaysia 5 oppurtunity infections: TB, PCP, toxoenceph, crypto mening,Bact pneumonia (Nissapatorn 2003)
According to Malaysia Ministry of Health Report year 2004; males remain the majority (93%) of reported HIV and AIDS cases (91%) within age group of 20 to 39 years. Malay teenagers and males involved in the drug addiction Another study in KL: most frequent routes of transmission were sexual contact (78.5%), followed by IDUs (30%), All females patients included in this study were a former wife to an intravenous drug users in which the virus transmission occurs through unprotected sexual relationship. This is due to poor knowledge regarding the relationship between drug addiction with HIV transmission and various routes of HIV/AIDS transmission in the community. Ignorance and being a naïve wife to those husbands involved with drug addiction also further increase HIV transmission.

The objective of this study is to identify the association between CD4 count with the site and type of intracranial lesions of opportunistic infections in HIV/AIDS patients.
Results of our study: All male patients were IV drug users. Late stage of HIV infection with a CD4 count <200><50.>< 50cells/µl presenting with non focal neurological symptoms of headache or altered behaviour. The CT findings were normal in 5 scans, cerebral atrophy in 1 scan and the rest had mass lesions.
Among 56 patients serological study for toxoplasmosis was done in 41 patients. Where by, 7 and 49 patients were in middle and late stage of the disease process respectively. This contribute to the high percentage of late stage patients with focal lesion as compared to those patients in middle stage of their illness (n=35 (71.4%) versus n=3 (42.9%) respectively).
No statistically significant correlation observed between intracranial lesions with clinical stage of disease in this study
--Professor Madya Dr. Hj. M. ABDUL KAREEM. USM, KUBANG KERIAN, KOTA BHARU, MALAYSIA

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  • The number of HIV cases in Malaysia in people aged 15 to 49 are 80,000 with its current rate of doubling every three years. In Malaysia, Cryptococcus is one of the leading opportunistic infections with advanced HIV infection. In predicting this, a useful guide is by monitoring the CD4 + T-Lymphocyte count. Neuroimaging plays a crucial role in establishing early intracranial involvement. The objective of this study is to identify the association between CD4 count with the site and type of intracranial lesions of cryptococcus infections in HIV/AIDS patients.
  • Ever since AIDS was first recognised as a Syndrome in 1981, counting the CD4 lymphocytes, or so-called T-4 cells (measured in cells per cubic millimetre), has played a pivotal role in AIDS, not just in charting the disease&apos;s progression, but also in determining everything from drug research to treatment guidelines, to the very definition of AIDS - who has it and who doesn&apos;t. One estimate has it that a CD4 count can fluctuate as much as 35 to 74 percent in a single day . One study demonstrated that T-cells decline with age. Children have much higher T-cell counts than adults and infants born to HIV-positive mothers have died even though their T-cells are over 1,000. Another recent study showed CD4 counts are markedly higher in women than in men and higher in smokers than in non-smokers. Even though individuals tend to hold their breath over every last T-cell, the laboratories that count them are far less precise. One study presented at the International Conference on AIDS in 1993 looked at the variations between CD4 counts from the same blood, different laboratories. Nine out of twenty-four patients studied had such different counts from the various labs that the results would lead to different treatment recommendations. Three out of those nine met the revised CDC/AIDS definition according to some lab results, but did not have AIDS according to others. A recent study in the Journal of the American Medical Association describes a group of HIV-positive people in Brazil who had very high CD4 counts-over 1,000-and still died of AIDS. They were all co-infected with another virus, HTLV-1 which causes a proliferation of CD4 cells. Throughout the study, their counts remained high - as high as 1,000 - and their health declined. The authors concluded that &quot;for this group, the higher mean CD4 lymphocyte count does not appear to offer immunologic benefit.&quot;
  • The mechanisms by which HIV induces susceptibility to opportunistic infections such as toxoplasmosis are likely multiple. These include depletion of CD4 T cells; impaired production of IL-2, IL-12, and IFN-gamma; and impaired cytotoxic T-lymphocyte activity.(12) Cells from HIV-infected patients exhibit decreased in vitro production of IL-12 and IFN-gamma, and decreased expression of CD154 in response to T gondii .(13-15) These deficiencies may play a role in the development of toxoplasmosis associated with HIV infection. First, the virus binds its envelope protein to CD4 and then that binding of CD4 to the envelope protein allows the envelope protein to bind to the second receptor, CCR5. The second receptor binding leads ultimately to the fusion process, whereby the viral membrane and the target cell membrane fuse. So there are two gateways for HIV-1 to enter cells: CD4 and one of the chemokine receptors, which in this case is CCR5. Earlier in that same year, Ed Berger had identified another chemokine receptor, CXCR4, which could also act as a second receptor for certain strains of HIV-1.
  • CD4 counts drop dramatically in people with HIV, in some cases down to zero. The ratio of CD4 cells to CD8 cells is often reported. This is calculated by dividing the CD4 value by the CD8 value. In healthy people, this ratio is between 0.9 and 1.9, meaning that there are about 1 to 2 CD4 cells for every CD8 cell. In people with HIV infection, this ratio drops dramatically, meaning that there are many times more CD8 cells than CD4 cells. Because the CD4 counts are so variable, some health care providers prefer to look at the CD4 percentages. These percentages refer to total lymphocytes. If your test reports CD4% = 34%, that means that 34% of your lymphocytes were CD4 cells. This percentage is more stable than the number of CD4 cells. The normal range is between 20% and 40%. A CD4 percentage below 14% indicates serious immune damage. It is a sign of AIDS in people with HIV infection. A recent study showed that the CD4% is a predictor of HIV disease progression. ------------- . Lymphocytes are a type of WBC that helps the body fight infection. Two main types of lymphocytes; B-lymphocytes and T-lymphocytes . T-lymphocytes/ T-cells (Thymus derived). There are two types of T-cells: CD4 Cells - These cells have molecules called CD4 on their surface. They start the immune response that protects the body from infectious invaders such as bacteria and viruses. CD8 Cells - These cells, with molecules on their surface called CD8, destroy other infected cells and produce antiviral substances that fight off infectious organisms. There are two primary types of T-cells. CD4 Cells - These cells have molecules called CD4 on its surface. These &quot;helper&quot; cells initiate the body&apos;s response to invading micro-organisms such as viruses. CD8 Cells - These types of T-cells have a molecule called CD8 on their surface. CD8 cells destroy cells that have been infected with foreign invading micro-organisms. CD8 cells also produce antiviral substances (antibodies) that help fight off the foreign invader. Normal Values: Lymphocytes make up 16-45% of white blood cells. Of those lymphocytes, about half are T cells, a quarter are B cells, and another quarter are natural killer cells. Helper T-cells, also known as absolute CD4+ or T4 count: more than 400 per microliter, or 32-68% of lymphocytes Suppressor T-cells, also known as absolute CD8+ or T8 count: 150-1000 per microliter There are several ways to count T cells and the normal range may vary with the method used. T-8 cells, (CD8+), are &quot;suppressor&quot; cells that end the immune response. also “killer” cells that kill cancer cells and cells infected with a virus. According to public health guidelines, preventive therapy should be started when an HIV-positive person who has no symptoms registers a CD4 count under 200. Some physicians will opt to consider treatment earlier, at 350. The Centers for Disease Control and Prevention considers HIV-infected persons who have CD4 counts below 200 to have AIDS, regardless of whether they are sick or well. CD4 antigen is the HIV receptor   The apparent specificity of CD4+ cell infection observed early in the history of HIV and AIDS, together with the observation that T4 cells are  depleted in disease (indeed, the course of disease in the patient is followed by CD4+ T cell levels), suggested that CD4 antigen might be the receptor for the virus. This was demonstrated by transfecting the CD4 antigen gene into CD4- human cells (such as cervical carcinoma HeLa cells) and showing that they acquired the property of being able to be infected by HIV (figure 16). CD4 antigen is the major receptor for both HIV-1 and HIV-2 in T4 cells and most other cells that can be infected by HIV. CD4 cell is an important part of the immune system. Indication Detecting HIV related Immune Deficiency Monitoring HIV Disease Used in combination with Plasma Viral Load Testing Efficacy Cell counts vary widely from lab to lab: Use the same lab to follow patients Diurnal cell count variation (from 50-150 cells/mcl): Time of day- CD4+ counts may be lower in the morning, fatigue, and stress can affect the test results. It&apos;s best to have blood drawn at the same time of day for each CD4 cell test,. Infections can have a large impact on CD4 cell counts. When your body fights an infection, the number of white blood cells (lymphocytes) goes up. CD4 and CD8 counts go up, too. Vaccinations can cause the same effects. Don&apos;t check your CD4 cells until a couple of weeks after you recover from an infection or get a vaccination. It may drop to 50% with acute co-morbid illness Normal: Non-HIV patients: 800-1200 cells/mcl Interpretation See HIV Course Each CD4 Count 10% rise decreases progression risk 15%
  • T gondii is recognized as a major cause of neurologic morbidity and mortality among patients with advanced HIV disease. *** In the AIDS population cerebral toxoplasmosis is the most common cause of brain abscesses, and B-cell lymphoma is the most common cause of brain neoplasm. However, toxoplasmosis occurs 2 to 3 times more frequently than lymphoma in AIDS patients AIDS is currently defined in persons older than 13 years as the presence of one of 25 conditions indicative of severe immunosuppression or HIV infection in an individual with a CD4+ cell count of less than 200 cells per cubic mm of blood. AIDS is the end point of an infection that is continuous, progressive and pathogenic There are about 33.2 million (estimate range: 30.6 million - 36.1 million) HIV-infected people in the world of whom about 22.5 million (range: 20.9 million - 24.3 million) are in sub-Saharan Africa where the adult infection prevalence is 5.9%. Approximately 14,000 new HIV infections occur daily around the world and over 90% of these are in developing countries. One thousand are in children less than 15 years of age. Of adult infections, 40% are in women and 15% in individuals of 15-25 years of age. Perinatal infection is now resulting in a large number of children being born with HIV. 30-50% of mother to child transmissions of HIV results from breast feeding and about a quarter of babies born to HIV-infected mothers are themselves infected. Asia-Pacific In 2006, about 1 million people in the Asia/Pacific region became infected by HIV and 630,000 people died. The total infected population in this region is an estimated 4.9 million (range 3.7 million - 6.7 million] people; of these, 2.1 million are age 15 to 24 years and 2.4 million are women (up 21% since 2004). In this region, HIV is increasing at a rate of 10% per year. In India, the infection rate is under 1% but this means that there were 5.1 million infected people which puts India behind only South Africa in total number of cases. Much of the Indian epidemic of HIV infection results from intravenous drug use. China also has a severe problem with up to 1.5 million HIV-infected people in 2004 (prevalence rate: 0.1%). It is predicted that if nothing is done to prevent the increasing infection rate, China will have 10 million cases by 2010. TE is the AIDS-defining diagnosis in 16% of AIDS patients. The prevalence rate in different provinces ranged from 0.3-11.8% in China. ***Acute toxoplasmosis is asymptomatic in 80-90% of healthy hosts. the acute infection rapidly progresses and may cause potentially lethal consequences. 225,000 cases of toxoplasmosis/year reported &amp;750 deaths, the third most common cause of lethal food-borne disease in USA Toxoplasmic encephalitis (TE) has been reported in 1-5% of AIDS In El Salvador and France, the seropositivity prevalence rate 75%. In France, 37% of AIDS patients have evidence of TE at autopsy. As many as 90% of adults in Paris are seropositive. Approximately 50% of the adult population in Germany is infected. In HIV-infected individuals, the seropositivity rate is approximately 50-78% in certain areas of Western Europe, Africa and South and Central America Toxoplasmosis. Approximately 70% of cerebral toxoplasmosis lesions are multifocal (15,16). Neurologic presentations include subacute headaches, fever, seizures, focal neurologic signs (12,13), and progressive dementia (17). Serology for toxoplasma frequently is positive, but specificity is low; only one third of cases show a rise in the titer of IgG antibody (18), and only 50% show intrathecal production of antibody to T gondii (19). Equally disappointing are the recent studies in polymerase chain reaction for T gondii in plasma and cerebrospinal fluid, which showed low sensitivity (20,21) and occasional false-positive results (22). Subsequent clinical response to antitoxoplasma therapy has been the main criterion for diagnosis.
  • In malaysia 5 oppurtunity infections: TB, PCP, toxoenceph, crypto mening,Bact pneumonia (Nissapatorn 2003)
  • MeA cross sectional study of 56 / 143 cases of HIV/AIDS patient thods and Materials: The study sample comprised of 56 adult HIV patients, with neurological deficit. CD4+T-lymphocyte count, Latex Agglutination Test for detection of Cryptococcus antigen and cranial axial CT scan were performed on all these patients as per the standard protocol. An experienced Radiologist analysed the images as regards to the site, number and nature of lesions. Sample size was calculated using Power and Sample software Where, P0 = proportion of presence of neurological symptoms in patient with positive scan = 0.373 p1 = proportion of absence of neurological symptoms in patient with positive CT scan = 0.627 α = 0.05 , m = 2 , = 80% = 0.8 Thus, sample size (n) = 45 power To include twenty five percent (25%) drop-out: Number of cases: 45 + 11 = 56
  • (Omnipaque (Iohexol) 300 mgI/ml or Ultravist (Iopromide) 300 mgI/ml).
  • Standardised brain window setting is used for filming, using window width (WW) of 80 – 100 HU and window level (WL) of 30-40 HU for optimum visualization of brain structures and intracranial pathology. A consultant radiologist who was not blinded to the history and clinical findings of the patients would review the cranial CT scan. However, the laboratory findings other than baseline blood investigations and HIV status are not provided
  • HIV tests The blood test performed for confirmation of HIV diagnosis are as listed below; At Hospital Raja Perempuan Zainab II (HRPZ II) - ELISA (enzyme-linked immunosorbent assay) test or EIA test ( enzyme immunoassay) done for screening. Partial Agglutination Test for confirmation. Using Roche Cobas Amplicator HIV-1 Monitor ™ Test, Version 1.5. At Hospital Universiti Sains Malaysia (HUSM) - ELISA test done for screening by using Abbott Axsym ™ System. Western-blot test for confirmation using Gene Laboratory Kit. CD4 count estimation- At HRPZ II- done by Immunocytometry System using Facs Count ™ Test, SEM-001 Becton Dickinson Machine. At HUSM- done using direct immuno-assay technique using Facs Calibre Machine. In GHKL, 1994-2001 in a study of 419 HIV PTS, CM was the fourth opp.infectn after TB, PCP AND TOXOPLAS. HUMAN INFECN UNCOMMON in healthy individuals. Third most frequent neurological complication in pts with AIDS after toxoplasmosis and AIDS dementia complex. CRYPTOCOCCUS NEOFORMANS: ENCAPSULATED YEAST LIKE FUNGUS 5-10% of AIDS pts acquired CNS cryptococcosis. Prevalence 2-4 %
  • According to Malaysia Ministry of Health Report year 2004; males remain the majority (93%) of reported HIV and AIDS cases (91%) within age group of 20 to 39 years. Malay teenagers and males involved in the drug addiction Another study in KL: most frequent routes of transmission were sexual contact (78.5%), followed by IDUs (30%), All females patients included in this study were a former wife to an intravenous drug users in which the virus transmission occurs through unprotected sexual relationship. This is due to poor knowledge regarding the relationship between drug addiction with HIV transmission and various routes of HIV/AIDS transmission in the community. Ignorance and being a naïve wife to those husbands involved with drug addiction also further increase HIV transmission.
  • Results: All male patients were IV drug users. Late stage of HIV infection with a CD4 count &lt;200 was found in 49. Blood sample could be obtained in 43 patients. Only 10 samples are positive for Cryptococcal neoformans . Simultaneous multiple opportunistic infections were found in 17 late stage patients with CD4 count &lt;50. In seropositive patients, lesions were in the parietal (60%), occipital (30%) lobes, midbrain (20%) and basal ganglia-thalamic region (10%). Multiple and single lesions were seen in equal proportion (50.0%).
  • Among 49 late stage patients, 41/49 (83.7%) had CD4 count less than 50 cells/µl.
  • In those 17 patients with multiple opportunistic organisms co-infection, all of them were late stage patients with CD4 count &lt; 50cells/µl presenting with non focal neurological symptoms of headache or altered behaviour. The CT findings were normal in 5 scans, cerebral atrophy in 1 scan and the rest had mass lesions. Among 56 patients serological study for toxoplasmosis was done in 41 patients. Positive sample for toxoplasmosis 29 In 29 patients with Toxoplasmosis , IgG antibody + in 23 (acute infection). Presence of both IgG and IgM in 3 Pts (denote acute and recently acquired or chronically infected)
  • Common intracranial manifesstations of CNS infecn includes meningitis, meningo- encephalitis, cryptococcoma. 5% of pts with cryptomeningitis had cryptococcoma.(range 5-25 %). Cryptococcomas do not have surroundimg edema; but, have thin rim of enhancement Gelatinous masses are hypo on T1 and hyper on T2. Though multiple lesions are typical, a solitary lesion occurs in nearly one third of patients (Wong.J, Quint.D.J, 1999). The size of the lesion usually less than 1 cm to over 3 cm associated with surrounding mass effect and edema of variable degree (Scott W Atlas, 2002).. Double dose delayed technique (using 200 ml of intravenous contrast by bolus or drip infusion with delayed scanning at 1 hour) has been found to be extremely effective in detection of these lesions as it permits maximal enhancement. The central portion of ring lesions of toxoplasma may fill in on delayed scans. Dina, T.S, 1991 also found delayed double-dose contrast material-enhanced CT increases the detection rate and conspicuity of lesions. White matter hypodensity – focal, multifocal or generalized reduction of the density of white matter region (normal HU is 28-35) due to localized accumulation of water in the white matter. Cerebral edema – indicates swelling of brain parenchyma due to an increase in its water content manifested by obscuration of lentiform nucleus, loss of insular ribbon sign and loss differentiation between cortex and subcortical white matter in early stage with diffuse parenchymal hypodensity and generalized effacement of the cerebral sulci on later stage. Brain atrophy - is described as diffuse ventricular enlargement with prominent sulci and no periventricular lucency. The callosal angle is more than 110°. Forty-one patient from the sample (n=56) were investigated for Toxoplasma antibody, in which 29 patients had positive antibody. Ten patients were tested positive for Cryptococcal antigen out of 43 samples taken. The distribution of various CT findings in patient with Toxoplasmosis and Cryptococcosis were presented in the Table 13 Toxoplasmosis characteristically appears as solitary or multiple iso- or hypodense lesions with ring- or nodular-enhancement pattern in contrasted scan. The ring enhancement is usually smooth but may be thick and irregular especially in larger lesion Porter et al found only 10% of lesions to be non-enhancing on a CT scan. 82% were peripherally enhancing (Mathew MJ, Chandy MJ, 1999). The lack of contrast enhancement may be due to the paucity of inflammation or less vigorous peripheral vascular proliferation. The median number of lesions detected in CT scan was 2 and in about 27% of patients the lesion was solitary (Mathew MJ, Chandy MJ, 1999). Acute communicating hydrocephalus was detected in one patient in whom both toxoplasma and cryptococcal blood serology were positive. This patient also had enhancement of basal cisterns and tentorium.
  • CM is slow progress dis, can be fulminant fatal, esp in transplant receipients and malignant pts. In Immunocompr pts the fungi form gelatinous lesions spreading from basal cysterns to br parenchyma. Via Virchow-Robin perivascular space as soap-bubble cysts lesions filled with organisms.
  • Mass lesion on CT in 10/43 cases.,mostly supratentorial esp in parietal lobes.
  • Hydrocephalus is the most frequent abnormality, either communicationg or NC. However ventricles may be normal in a combination of increased ICP and cerebral edema.c* may increase in &gt;50% of HIV patients with CM without hydrocephalus or cerbral edema.It may be due to failure of csf ABSORPTION.Blindness is the mostb serious complication due to &gt;ICP,direct invasion of optic nerve, arachnoiditis.
  • In normal patient with brain abscess secondary to hematogenous spread, the intracranial lesion distribution with approximate decreasing order of frequency involved the frontal≈ temporal &gt; frontoparietal &gt; parietal &gt; cerebellar &gt; occipital. (Mandell, Douglas, Bennet, Principles and Practice of Infectious Disease Textbook, Third Edition, Churchill Livingstone, 1990).
  • However, our observation of multiple lesions, supratentorial location and lobar distribution of toxoplasmosis lesions are in agreement with their study. Presence of more lesions in the parietal lobe can be explained by the facts that parietal lobes received the highest regional blood flow through the middle cerebral arteries. This is followed by frontal lobe which received blood supply from the anterior cerebral artery.
  • 5.2.11 Relationship between CD4 count with intracranial lesions: CM usually affects patients with CD4 count of less than 100 cells/ μ l Significant unequal proportion of patients was observed in this study. Where by, 7 and 49 patients were in middle and late stage of the disease process respectively. This contribute to the high percentage of late stage patients with focal lesion as compared to those patients in middle stage of their illness (n=35 (71.4%) versus n=3 (42.9%) respectively). No statistically significant correlation observed between intracranial lesions with clinical stage of disease in this study (Table 16).
  • primary CNS lymphoma is indistinguishable from toxoplasmosis (Dina.T.S, 1991). Thus, in appropriate clinic setting where prevalence of Toxoplasmosis is high, empiric treatment of focal enhancing CNS lesion with anti-Toxoplasma therapy were warranted in most cases without prior biopsy. In toxoplasmosis patients, improvement is usually evident clinically and on CT scans in 1-2 weeks. If there is no clinical or imaging response to therapy, then biopsy should be considered. No comparison can be made in lesion distribution between immunocompetent and immunocompromised patients. This is because severe manifestations of toxoplasmosis in person with normal immune function are rare. The reports of this condition were scarce and largely unknown. Toxoplasmosis in an immunocompromised patient was usually due to reactivation of latent form of infection. The primary infection is usually asymptomatic or unrecognized. Mc Cabe et al., 1987 has described the most common recognized findings is cervical lymphadenopathy which is usually painless and sometimes accompanied by low grade fever (Schwartzman, 2001). Krick and Remington, 1978 has described a mononucleosis-like syndrome characterized by fever, headache, malaise, lymphadenopathy, hepatosplenomegaly, myalgia and atypical lymphocytosis which develops within 1-3 weeks after exposures to infectious material (Schwartzman, 2001). Other reported manifestations were pneumonitis, myocarditis, meningoencephalities, polymyositis and systemic disease leading to death (Schwartzman, 2001). There are also no association found between toxoplasmosis and cryptococcosis with clinical stage of the disease. - Similarly, no association (p value &gt; 0.05) was detected between intracranial lesions with clinical stage of disease as reflected by CD4 count &quot;I do think that, generally, there is a correlation between a decline in CD4s and a decline in health, but that is not always the case,&quot; Says Harris, referring to the new CDC definition of AIDS, &quot;The 200 cut off point really screws over a lot of people who have just over 200 CD4 cells and are quite sick, and conversely, it makes people who have less than 200 feel they&apos;re dying, when they may have ten or more years of health in front of them”. I think we&apos;ve made the mistake of attributing everything under the sun to CD4 levels, basically because we had a paucity of information,&quot; says Harris. ----------------------- Since about 30.4% subjects had co-infection the exact pathology which is predominant is difficult to determine. In our study, Cryptococcus fungal infections correlated well with the mean CD4 counts in our patients. No statistically significant correlation was found between various sites of intracranial cryptococcus lesions with clinical stage of disease in this study.
  • The clinical practice guidelines (CPG) by Malaysia Ministry of Health, 2006, also stated that CD4/CD8 count should be regularly monitored in every 4 or 6 months depends on the viral loads.
  • involvement of the lung (84%), the brain continued to be the second most frequently affected organ (63%), followed by the adrenal glands (44%) (Jellinger et al. 2000 Involvement of the central nervous system in AIDS …. affecting between 40 – 75% of patients ( Bensalem MK, Berger JR, 2002 ). The response of the brain to pathogens in AIDS patient differs from that in immunocompetent individuals. Because of the atypical reaction, the usual imaging criteria for intracranial lesions may be altered and are not diagnostically pathognomonic. CD4 count was very much helpful in predicting causative organisms. However this must be supported with other laboratory findings for ultimate diagnosis of a given patient. During the last years, changing patterns of both organ and systemic pathology have been observed in AIDS, due to highly active antiretroviral therapy (HAART). HIV-1 most likely enters the CNS in an infected macrophage. Infected microglial cells and astrocytes in the brain will release cytokines namely TNF-α, IL-1 and IL-6 which may amplify HIV-1 multiplication in macrophages. Microglia and macrophages release toxic viral components and quinolinic acid causing damage to the neurons. This cycle of immune activation within the brain parenchyma is most likely leads to an increased viral burden as well as to the broad spectrum of neurological disease caused by HIV-1infection in the brain (Figure 3 ). No comparison can be made in lesion distribution between immunocompetent and immunocompromised patients. This is because severe manifestations of toxoplasmosis in person with normal immune function are rare. The reports of this condition were scarce and largely unknown. Toxoplasmosis in an immunocompromised patient was usually due to reactivation of latent form of infection. The primary infection is usually asymptomatic or unrecognized. Mc Cabe et al., 1987 has described the most common recognized findings is cervical lymphadenopathy which is usually painless and sometimes accompanied by low grade fever (Schwartzman, 2001).
  • Toxoplasma gondii TGis an obligate intracellular protozoan Transmission to humans: meat vege, cat Diffuse TE form may manifest acutely and can be rapidly fatal chronically infected individual manifests as toxoplasmic encephalitis. characterized by the persistence of the organism in tissues of the infected individual (primarily brain, skeletal muscle, and heart). cell-mediated immunity after acute infection with T gondii results in control but not eradication of the infection. A chronically infected individual who develops defects in cell-mediated immunity is at risk for reactivation of the infection. Toxoplasmosis in this setting manifests primarily as toxoplasmic encephalitis. chronic or latent phase of infection is characterized by the persistence of the organism in tissues of the infected individual (primarily brain, skeletal muscle, and heart). This seroprevalence even was much higher compared to other studies eg.15-37% in France, 21% in Malaysia, 22.45 in Thailand or 10-40% in USA (V. Nissapatorn et all, 2003). --------- As of December 2005, 984,155 Americans had been reported with AIDS (up from 641,086 in 1996). Adult and adolescent AIDS cases total 943,525 with 761,723 cases in males and 181,802 cases in females (figure 10B). Through the same time period, 9,101 AIDS cases were estimated in children under age 13. Cells of the nervous system HIV infects oligodendrocytes, astrocytes, neurones, glial cells and brain macrophages. Macrophage-tropic forms are found in the cerebro-spinal fluid. HIV causes disease of the central nervous system  which may result from the small protein, Tat, that is encoded by the virus and which acts as a general transactivator of transcription. This protein binds to neural cells via CD91 antigen and is internalized. As a result, cell metabolism is affected (such as nitric oxide signaling). HIV is also thought to compromise blood-retinal barrier integrity. HIV in the brain and in the cerebro-spinal fluid may be particularly resistant to chemotherapy because of the failure of anti-retroviral drugs to penetrate the blood-brain barrier. Clinical findings are altered mental state, seizures, weakness, cranial nerve disturbances, sensory abnormalities, cerebellar signs, meningismus, movement disorders, and neuropsychiatric manifestations. The characteristic presentation is usually a subacute onset with focal neurologic abnormalities in 58-89% of patients. However, in 15-25% of cases, the clinical presentation may be more abrupt, with seizures or cerebral hemorrhage. Most commonly, hemiparesis, speech abnormality, or both are the major initial manifestation. Brain stem involvement often produces cranial nerve lesions, and many patients exhibit cerebral dysfunction with disorientation, altered mental state, lethargy, and coma. Less commonly, parkinsonism, focal dystonia, rubral tremor, hemichorea-hemiballismus, panhypopituitarism, diabetes insipidus, or the syndrome of inappropriate antidiuretic hormone secretion may dominate the clinical picture. T gondii serology: to identify HIV patients at risk for developing toxoplasmos. 97% - 100% of HIV-infected patients with TE have anti- T gondii IgG antibodies . Thus, the absence of antibodies against T gondii makes the diagnosis of toxoplasmosis unlikely in these patients. PCR-based detection of T gondii DNA in CSF has a sensitivity that varies from 12% to 70% (usually 50-60%) and a specificity of approximately 100% in patients with toxoplasmic encephalitis PCR in blood samples has a low sensitivity . T gondii isolation from cultures of body fluids (blood, CSF, bronchoalveolar lavage fluid) or tissue biopsy specimen in the appropriate clinical setting. up to 6 weeks of culture may be required. Cerebrospinal fluid (CSF) from patients with toxoplasmic encephalitis may reveal mild pleocytosis of mononuclear predominance and protein elevation.(1) Intrathecal production of anti- T gondii IgG can be calculated with the following formula: Most patients with AIDS-associated toxoplasmosis in the United States lack detectable anti- T gondii IgM antibodies because the illness represents reactivation of a chronic infection A ratio &gt;1 indicates intrathecal production of anti- T gondii IgG and supports the diagnosis of toxoplasmic encephalitis.(1) Caution should be exercised when considering lumbar puncture due to the risk of brain herniation if mass effect is present. PCR can also be positive in bronchoalveolar lavage fluid and vitreous and aqueous humor of HIV-infected patients with toxoplasmosis. A positive PCR in brain tissue does not necessarily indicate active infection because tissue cysts persist in the brain long after acute infection. Detection of T gondii DNA in amniotic fluid enables diagnosis of intrauterine infection.(31)
  • HIV is a retrovirus spherical, three-layered structure measuring 80-130 nm in diameter It composed of two copies of single-stranded RNA enclosed by a conical capsid, which is in turn surrounded by a plasma membrane that is formed from part of the host-cell membrane. Both types of HIV are quite similar, in which they have three major genes coding (gag, pol,env) for structural proteins with some subtype-specific genes. Surface glycoprotein Gp160 is encoded by the env (envelope) gene. Gp160 is cleaved after translation by host enzymes in the Golgi Body to form Gp120 (SU) and Gp41 (TM). Gp 41 is embedded in the membrane, Gp120 is not but is held to Gp41 by non-covalent interactions (figure 14). It is easily shed from the virus particle. Note: Gp120 and Gp41 are made from a single polypeptide. There is a large number of sugar chains on gp120 (which may pose a problem for a vaccine) . Gp120 is the protein that interacts with a receptor on the cell to be infected. Gp41 is the fusogen that is exposed after Gp120 has bound to the cell.
  • nearly all HIV-infected persons have detectable antibody 6 months after the infection. Primary or acute infection is a rapid rise in plasma viremia which immediately follows the exposure to HIV. 80 to 90% develop an acute retroviral syndrome (ARS) characterized by flu-like symptoms of fever, malaise, lymphadenopathy, pharyngitis, headache, myalgia, and sometimes a rash. Onset occurs within a few weeks of infection and the syndrome generally resolves within two weeks. Following ARS, with average of three weeks, seroconversion occurs as antibody levels begin to rise and nearly all HIV-infected persons have detectable antibody 6 months after the infection. Clinical Latency: A strong immune defense reduces the number of viral particles in the blood stream, Clinical latency can vary between two weeks and 20 years. During this early phase of infection, HIV is active within lymphoid organs, virus become trapped in the follicular dendritic cells (FDC) network. The surrounding tissues that are rich in CD4+ T-cells also become infected, and viral particles accumulate both in infected cells and as free virus. Individuals who have entered into this phase are still infectious. AIDS AIDS is the most severe manifestation of HIV infection where the cellular immunity has lost, the CD4+ T cells &lt; 200 per µl blood. individuals are prone for oppurtunistic infection and tumors.. In the absence of antiretroviral therapy, the median time of progression from HIV infection to AIDS is nine to ten years , and the median survival time after developing AIDS is only 9.2 months . However, the rate of clinical disease progression varies widely between individuals, from two weeks up to 20 years. Other markers of immune status -- such as serum neopterin, beta-2 microglobulin, HIV p24 antigen, soluble interleukin-2 receptors, immunoglobulin A, and delayed-type hypersensitivity (DTH) skin-test reactions -- may be useful in the evaluation of individual patients but are not as strongly predictive of disease progression or as specific for HIV-related immunosuppression as measures of CD4+ T-lymphocytes (14-21, 31).
  • MeA cross sectional study of 56 / 143 cases of HIV/AIDS patient thods and Materials: The study sample comprised of 56 adult HIV patients, with neurological deficit. CD4+T-lymphocyte count, Latex Agglutination Test for detection of Cryptococcus antigen and cranial axial CT scan were performed on all these patients as per the standard protocol. An experienced Radiologist analysed the images as regards to the site, number and nature of lesions. Sample size was calculated using Power and Sample software Where, P0 = proportion of presence of neurological symptoms in patient with positive scan = 0.373 p1 = proportion of absence of neurological symptoms in patient with positive CT scan = 0.627 α = 0.05 , m = 2 , = 80% = 0.8 Thus, sample size (n) = 45 power To include twenty five percent (25%) drop-out: Number of cases: 45 + 11 = 56
  • Transcript

    • 1. Does CD4 Cell Count Influence Computed Tomography (CT)scan imaging features of Intracranial Opportunistic Infections(OI) lesions in adult HIV/ AIDS patients? Abdul Kareem M*, siti jusna * Arif Abas** Mahiran Mustapha** AAhmad Munawir *** • AP, Department of Radiology, School of Health Sciences, Universiti Sains Malaysia, 16150- Kubang Kerian, Kota Bharu, Kelantan, Malaysia • ** HOD,Hospital Raja Perempuan Zainab II(HRPZ II) Kota Bharu, Kelantan, Malaysia. • Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, (c) mkareem 1 • Kelantan.
    • 2. "People have been terrorised by these CD4 T-cell counts,” (ack) (c) mkareem 2
    • 3.  The CD4+ T-lymphocyte is the primary target for HIV. because of the affinity of the virus for the CD4 surface marker. In HIV infection, CD4+ T cells are infected and they present viral proteins and then are lysed by cytotoxic cells such as CD8+ T lymphocytes As more and more CD4+ T cells are destroyed, the number of CD4+ T- lymphocytes decreases, immune function falls and the risk and severity of opportunistic illnesses increase. (c) mkareem 3
    • 4. CD4 / T-4 cells / T-lymphocytes/ T "helper"cells are a type of lymphocyte (WBC) withCD4 molecules specific proteins on itssurface.It leads the attack against infections. Normal CD4 counts : 500 – 1600/µl CD8 counts are between 375 and 1100. The ratio of CD4 cells to CD8 0.9 - 1.9 . CD4 percentage is 20% - 40%. refers to total lymphocytes. more stable- A CD4% < 14% is a sign of AIDS in HIV infection. (c) mkareem 4
    • 5.  2006: 4.3 million newly infected with HIV > 95% of these are in low and middle income countries.. 14,000/day become newly infected with HIV. Of these, half are women and 40% are young people (15-24 years old). Of the estimated 37 million adults HIV worldwide 7.2 m pts in SEA. AIDS is now a leading cause of death worldwide 630,000 died in 2006 3.1M DEATHS IN CHILDREN Kelantan recorded the highest number(596) of HIV/AIDS. As one-third of AIDSpatients develop neurological complications,this study focuses on cranial CT features andits association with CD4 count. (c) mkareem 5
    • 6. Aims and ObjectivesGeneral Objectives1. To categorise HIV patients basing CD4 count2. To study CT scan features of intracranial Opportunistic infections(OI) in HIV patientsSpecific ObjectiveTo assess the relationship between cranial CT scanfindings intracranial Opportunistic infections(OI) and CD4 count in HIV patients (c) mkareem 6
    • 7. Null HypothesisThere is no correlation/ relationshipbetween cranial CT scan findings ofintracranial Opportunistic infections(OI)and CD4 count in HIV patients (c) mkareem 7
    • 8. Methodology: Inclusion Criteria 12 years old and above HIV/AIDS patient with neurological symptoms All patients who had cranial NECT and CECT. All patients who had CD4 count done within 1 month of CT scan examination.Exclusion Criteria HIV/AIDS patients whose cranial CT was for trauma related neurological complaints HIV/AIDS patient undergone cranial CT scan but without CD4 count 4. HIV/AIDS patient had undergone only cranial NECT scan (c) mkareem 8
    • 9. Methodology: Technique 1. Patient fasted for 4-6 hr 2. steroid cover if H/O allergy, asthma 3. Removal of metal objects (eg.earring, hair pin) 4. CT: Axial Images from skull base to vertex 5. NCCT and 6. CECT: 50 ml of non-ionic I.V.CM was usedTotal number of patients needed: 56Site: In Hospital Raja Perempuan Zainab II (HRPZ II) and HUSM (c) mkareem 9
    • 10. Methodology: Technique . Below are the technical parametn this study: SupinePatient positionArea of interest/study From foramen magnum to the skull vertexGantry tilt 10 degree caudad angulation to the occipitomeatal baseline (OMBL) to reduce exposure to the lenses Range 1: base of foramen magnum to pituitary fossa (Slice thickness of 4.0mm) Range 2: pituitary fossa to cover the entire cerebrum (Slice thickness of 8.0mm)X-ray tube voltage (kV) 120-140Tube current (mAs) 220-260Pitch 1.5Algorithm Volume artifact reduction (VAR)Kernel AH 40Increment 2Feed 3Direction Caudo-cranialDelay Start scan at the end of contrast injection (c) mkareem 10
    • 11. Blood test: confirmation of HIV and OI (Cryptococcosis & Toxoplasmosis) ELISA (enzyme-linked immunosorbent assay) test or EIA test ( enzyme immunoassay) done for HIV screening. Partial Agglutination / Western-blot test for confirmation using Gene Laboratory Kit. 43 blood samples for detection of Cryptococcal antigen. Out of 43, ten were positive.(about 20%) All are late stage HIV. Latex agglutination test using Murex Kit was used for detection of serum cryptococcal antigenCD4 count estimation- At HRPZ II- done by Immunocytometry System using Facs Count ™ Test, SEM-001 Becton Dickinson Machine. At HUSM- done using direct immuno-assay technique using Facs Calibre Machine. (c) mkareem 11
    • 12. Result: Demographic features Histogram 20  Among 56 patients:  48 males (85.7%) 15  8 females (14.3%).  Malays =53 (94.6 %)Frequency  Chinese = 3 ( 5.4% ) 10  Mostly in fourth decade (55.36%).  youngest 22 year old 5  eldest was 66 year old.  mean age 34.25 years Mean = 34.25 0 Std. Dev. = 7.317 N = 56  standard deviation < 7.3 20 30 40 50 60 70 ageAge distribution ** All the male patients in this study were intravenous drug users (whether active or former drug addict). (c) mkareem 12
    • 13. Objective N0 – 1: To categorise HIV patients basing CD4 count Stage CD4 count (cells/µl) No of patient Early ≥ 500 Nil Middle 200 - 499 7 Late ≤ 200 49 87.5% in the late stage of disease 41 patients have CD4 < 50cells/µl (73.2%) CD4: minimum - 1 maximum -452cells/µl. (mean57.8) standard deviation less than 99.8. ** None in their early stage of illness. (c) mkareem 13
    • 14. 5.36% 1.79% n=3 n=1 5.36% n=3 1.79% n=1 cd4subca tegory <50 50-99 100-199 12.50% 200-299 n=7 300-399 400-499 Pies show counts 73.21% n=41 cd4subca tegory <50 50-99 100-199 200-299 300-399 CD4 subcategory 400-499 Pies show counts (c) mkareem 14%
    • 15. Result: Opportunistic organisms. Positive sample for Toxoplasmosis 29 /41 Positive for Cryptococcosis 10/43 Mixed infections: 17 patients (30.4%) had 9 patients with tuberculosis were positive for toxoplasma, 4 patients + both for toxoplasma and cryptococcus, 2 patients had cryptococcus with tuberculosis another 2 patients toxoplasma, cryptococcus and TB (c) mkareem 15
    • 16. Morphology of CT lesion Toxoplasma antibody Cryptococcal positive (n=29) antibody positive (n=10)Ring-enhancing lesion 9 2Nodular lesion 3 2White matter 19 5hypodensity i.focal 4 1 ii.multifocal 15 4Diffuse cerebral edema 12 4Hydrocephalus 1 1Meningeal enhancement 9 2Normal scan 7 3Multiple lesions 20 3 Morphology of CT lesion (c) mkareem 16
    • 17. : Meningeal enhancement with white matter edema  CM form predominates  Negative CT doesn’t exclude CM  Best seen on MRI  Usually involve sylvian F & Basal ganglia  Serum cryptococ antigen is + in >99% of AIDS related CM. (c) mkareem 17
    • 18. Nodular lesionSingle Multiple (c) mkareem 18
    • 19. (c) mkareem 19
    • 20. Ring lesion (c) mkareem 20
    • 21. White matter edema (c) mkareem 21
    • 22. Cerebral atrophyHydrocephalus- 1 (mild) (c) mkareem 22
    • 23. Association between cryptococcosis & site of intracranial lesion in our study The cerebrum was significantly affected in 60.0%. involve the parietal (40.0%), occipital (30.0%), frontal (0%) and temporal (10.0%) lobes. Basal ganglia and thalamus only in 10.0% Midbrain in 20.0% cerebellum in 0.0% . Multiple lesions were:30% No significant correlation observed between cryptococcosis with various site of intracranial lesion in this study Crypto: site of predilection: BG, Thalam & Midbr. (c) mkareem 23
    • 24. Site of lesion cryptococcus(n = 43) p-value X2 Positive n=10(%) Negative n=33(%)Cerebral hemisphere 20 (60.6%) 0.001 (1) 0.973 b Present 6 (60.0%) 13 (39.4%) Absent 4 (40.0%)Frontal lobe 12 (36.4%) 5.044893 (1) 0.025 b Present 0 (0%) 21 (63.6%) Absent 10 (100.0%)Parietal lobe 15 (45.5%) 0.093 (1) 0.761 b Present 4 (40.0%) 18 (54.5%) Absent 6 (60.0%)Temporal lobe 6 (18.2%) 0.377 (1) 0.539 bPresent 1 (10.0%) 27 (81.8%) Absent 9 (90.0%)Occipital lobe Present 3 (30.0%) 12 (36.4%) 0.137 (1) 0.711 b Absent 7 (70.0%) 21 (63.6%)Basal ganglia-thalamic 12 (36,4%) 2.529 (1) 0.112 blesions Present 1 (10.0%) 21 (63.6%) Absent 9 (90.0%)Cerebellum Present 0 (0.0%) 1 (3.0%) - 1.000a Absent 10 (100.0%) 32 (97.0%)Brainstem (midbrain) 0.0132 (1) 0.716b Present 2 (20.0%) 5(15.2%) - 1.000a Absent 8 (80.0%) 28 (84.8%)Multiple lesions Present 3 (30.0%) 15 (45.5%) 0.638a Absent 7 (70.0%) 18 (54.50%) a Fisher’s Exact Test (c) mkareem 24 b Pearson Chi-square Test
    • 25. Association between clinical stages with cryptococcal serology Clinical stage of diseaseToxoplasma serology Late stage Middle stage(n=43) (CD4< 200cells/µl) (CD4 200-499cells/µl) X2 (df) p-value _ Positive (n=10) 10 (100.6%) 0 (0%) 0.320a Negative (n=33) 28 (84.8%) 2 (15.2%) a Fisher’s Exact Test (c) mkareem 25
    • 26. Association between clinical stagesof disease with Toxoplasma serology Clinical stage of diseaseToxoplasma serology Late stage Middle stage(n=41) (CD4< 200cells/µl) (CD4 200-499cells/µl) X2 (df) p-value _ Positive (n=29) 28 (96.6%) 1 (3.4%) 0.200a Negative (n=12) 10 (83.3%) 2 (16.7%)a Fisher’s Exact Test (c) mkareem 26
    • 27. Association of intracranial lesions to CD4 countIntracranial Late stage Middle stage X2 (df) p-value lesion CD4< 200cells/µl CD4 200-499cells/µl (%) (%)Focal lesion - 0.195a Present 71.4% 42.9% Absent 28.6% 57.1%Atrophy 0.242(1) 0.622 b Present 22.4% 14.3% Absent 77.6% 85.7%Combination 0.023(1) 0.879 b Present 12.2% 14.3% Absent 87.8% 85.7% a Fisher’s Exact Test b Pearson Chi-square Test (c) mkareem 27
    • 28. Conclusion None of the patient was in their early stage HIV. 100% of cryptococcus pts were in late stage The CD4 count ranges: 1 - 452cells/µl. The mean count was 57.8. CD4 count was very much helpful in predicting the stage of HIV and causative organisms. (c) mkareem 28
    • 29. Problems and limitations 1. Interhospital transfer –CT films were given away to the district hospital when patients were transferred. No PACS inGH Untraceable CT films – No proper recording system. Many CT films are missing from infectious disease clinic or radiology department storage room at HRPZ II. Co-infection of multiple opportunistic infections – presence of other multiple opportunistic infections in a given patient giving rise to atypical or non-specific CT findings. Imaging modality – CT is known to have low sensitivity in demonstrating the lesion as compared to MRI. This factor for example, might affect the detection of ring lesion in this study. (c) mkareem 29
    • 30. Problems and limitations CD4 count –measurement only be performed on certain days. CT scan usually was performed on the day of admission. Thus if CT scan was ordered within that period, the CD4 count might be beyond one month period of the scan. While waiting, several newly diagnosed patients died before CD4 count was performed (c) mkareem 30
    • 31. Recommendations Severe immunosuppression in HIV/AIDS predisposed the patients to multiple types of infections. The purpose of this study is to simply predict the intracranial sites commonly involved in HIV/AIDS patients. However, since multiple cerebral infections can co-exist at a given time, the CT scan findings varied enormously.We suggest the following; Another study to be carried out with larger sample size. Written guidelines should be provided to the physician so that consistent history taking, physical examination and Base line laboratory results of the patients can be achieved. Further characterization of suspicious lesions should be done using MRI Biopsy of lesion should be considered if the laboratory and imaging findings are inconclusive. (c) mkareem 31
    • 32. References1. Alexander, S., Mark, Atlas, S., W., (1989). Progressive Multifocal Leukoencephalopathy in Patients with AIDS: Appearance on MR Images.Neuroradiology, 173:517-520.2. AIDS Epidemic Update, December (2005).3. Ackermann, H-W., Bertiaume, L., Tremblay, M.,(2001) Viral Pathogens in Diagrams. CRC Press.4. Balakrishnan, J., Becker,P., S., Kumar, A., J., Zinreich, S., J., McArthur,J., C., Bryan, R., N.,(1990).Acquired Immunodeficiency Syndrome: Correlation of Radiologic and Pathologic Findings in the Brain. Radiographics, 10:201-215.5. Barber,C., J., Rowlands, P., C., McCarty, M., Choudhri, H., Stevens, J., M.,(1990). Clinical Utility of Cranial CT in HIV Positive and AIDS Patients with Neurological Disease. Clinical Radiology, 42:164-165.6. Belman,A.,L.,(2002) HIV-1 infection and AIDS, Neurologic Clinics.Volume 20, Number 4,W.B.Saunders Company.7. Cohen .P., T.( 1996). The AIDSs Knowledge Based Textbook, Second Edition, Little Brown.8. Connor, M.,D., Lammie, G., A., Bell, J., E., Warlow, C., P., Simmonds, P., Brettle, R., D.(2003) Cerebral Infarction in Adult AIDS patients: Observations From the Edinburgh HIV Autopsy Cohort. Stroke, 31:2117-2126.9. Nissapatorn. V, Lee. C, Fatt. Q.K., Abdullah. K.A (2003). AIDS-Related Opportunistic Infections in Hospital Kuala Lumpur. Jpn.J.Infect.Dis., 56.187-192.10. Nissapatorn. V, Lee. C, Fatt. Q.K., Abdullah. K.A.,Leong .C. L, Mahmud. R. (2004). Toxoplasmosis in HIV/AIDS Patients: Current Situation. Jpn.J.Infect.Dis., 57.160-165.11. Nissapatorn. V, Lee. C, Abdullah. K.A., Mahmud. R. (2004). Spectrum of opportunistic infections among HIV-infected patients in Malaysia. Southeast Asian J Trop Med Public Health. 35:26-32.12. Mohamad Z., Naing N.N.(2004). Characteristic of HIV-infected tuberculosis patients in Kota Bharu Hospital, Kelantan from 1998 to 2001. Southeast Asian J Trop Med Public Health. 35:140-3..13. Nissapatorn. V, Lee. C, Ithol. I, Yik. F.M., Abdullah. K. A. (2003). Tuberculosis In AIDS Patients. Malaysia Journal of Medical Sciences, Vol 10, No 1:60-64.14. Federle, M., P, (1988) A Radiologist Looks at Aids: Imaging Evaluation Based on Symptom Complexes.Radiology, 166:553-562.15. Cheong I., Lim. A.,Lee. C., Ibrahim. Z., Sarvanathan.K.(1997). Epidemiology and clinical characteristics of HIV-infected patients in Kuala Lumpur. Med J Malaysia. 52:313-7.16. Ismail.R., Doi. S., Naganathna. N (1995). HIV infection in Malaysia: a report of cases at the University Hospital, Kuala Lumpur. Med J Malaysia. 50:298-301.17. of Central Nervous System Infections. Seminar in Roentgenology, VolXXXIV, No 2 (April): 123-143.18. Wig.N., Wali.J.P.(2000). Central Nervous System and HIV/AIDS. Journal of Indian Academy of Clinical Medicine.Vol 5; No 2:163-168.19. Stevens.D.A., Denning.D. W., Shatsky.s., Armstrong. R.W., Adler. J. D., Lewis.B.H.(1999). Cryptococcal meningitis in the immunocompromised host: intracranial hypertension and other complication. Mycopathologia.146:1-8.20. . (c) mkareem 32
    • 33. References20 Lorenzo. G.D., Pagano. M., Garau. M.L., Deri. N., Cahn.P., Perez.H., Pagano.M.A.21. (2005). Units of Neurology and Section of Infectious Diseases, Fernandez Hospital, Buemous Aires, Argentina. Neuroimaging findings in cerebral toxoplasmosis (CT) in AIDS patients (Poster abstracts).22. Graham III, C., B., Wippold II, F., J., Pilgram, T., K., Fisher, E., J., Smoker, W., R., K.,(2000). Screening CT of the Brain Determined by CD4 Count in HIV- Positive Patients Presenting with Headache. AJNR Am J Neuroradiol, 21:451-454.23. Graham III, C.,B.,Wippold II, F., J.(2001) Headache in the HIV patient: A review with special attention to the role of imaging. Cephalalgia, 21:169-174.24. Gilliams., A., R., Allen, E., Hrieb, K., Venna, N., Craven, D., Carter, A., P.,(1997) Cerebral Infarction in Patients with AIDS. AJNR Am J Neuroradiol, 18:1581- 1585.25. Gifford, A., L., Frederick, M., Hecht,(2001). Evaluating HIV-infected Patients With Headache: Who Needs Computed Tomography?. Headache, 41:441-448.26. Schutte.C.M., (2001). Clinical Cerebrospinal Fluid and Pathological Findings and Outcomes in HIV-Positive and HIV-Negative Patients with Tuberculous Meningitis. Infection, 29: 213-217.27. Whiteman.M., Espinoza. L., Post. M.J.D., Bell. M. D., Falcone. S. (1995). Central Nervous system Tuberculosis in HIV-Infected Patients: Clinical and Radiographic Findings. AJNR Am J Neuroradiol 16:1319-1327.28. Thwaites. G.E., Hien. T. T. (2005). Tuberculous meningitis:many question, too few answers. Lancet Neuro. 4:160-70.29. Engin.G., Acunas. B., Acunas. B., Tunaci. M. (2000). Imaging of Extrapulmonary Tuberculosis. Radiographics. 20:471-488.30. Harisinghani.M.G., McLoud. T. c., Shepad.J.A.O., Ko.j.P., Shroff.M.M., Muller.P.R.(2000). Tuberculosis from Head to Toe. Radiographics;20:449-470.31. Whelan.M.a., Stern. J. (1981). Intracranial Tuberculoma. Radiology 138:75-81.32. Cornell.S.H., Jacoby. C.G. (1982). The varied Computed Tomographic Appearance of Intracranial Cryptococcosis. Radiology.143:703-707.33. Popovich. M. J., Arthur.R.H., Helmer. E. (1989). CT of Intracranial Cryptococcosis. AJR; 154 (March):603-606.34. Harrison. T. S (2000). Cryptococcus neoformans and Cryptococcosis. Journal of Infection. 41:12-17.35. Portocarrero.J.S., Cecilia. E. P. (1997). Intracerebral mass lesions in Patients eith Human Immunodeficiency Virus Infection and Cryptococcal Meningitis. Case report. Diag Microbiol Infect Dis. 29:193-198.36. Schwartzman.J.D. (2001). Toxoplasmosis. Principles and Practice of Clinical Parasitology. John Wiley & Sons Ltd.37. Wong.J., Quint.d. J.(1999). Imaging (c) mkareem 33
    • 34. (c) mkareem 34
    • 35. Pathogenesis in the brain Indeed, postmortem neuro-pathological series reveal that CNS abnormalities occur in up to 90% of patient with advanced AIDS (Connor et al, 2006). Brain parenchyma  CSF (and reverse)  Infection of stromal cells, macrophages, endothelial cell and choroids plexus . ependymal & subependymal cells Damage to the nervous system via 3 ways: i. Direct infection/ killing or alteration of cellular metabolic function (cytopathic effects). The retention of viral genome in neural cells in a persistent latent form  cell dysfunction. ii. cytotoxic action of HIV-specific products or aberrantly secreted cellular products In addition, autoimmune mechanisms and such factors as virus strain may also play a role in nervous system dysfunction. (c) mkareem 35
    • 36. Clinical Variables: A • Sex – male or female B. Age – age recorded to the nearest year C. Neurological signs and symptoms - Signs - GCS, fever, neck stiffness and neurological findings. Symptoms:-hemiplFocal:egia, hemiparesis, slurred speech, CN palsy ii). Nonfocal symptoms-headache, seizure, abnormal behaviour, altered sensorium D • CD4 count – A/C to 1993 revised CDC classification systems, Category 1 (early stage, CD4 ≥ 500cells/µl) , category 2: (middle stage, CD4 200-499cells/ µl) and category 3 (late stage, CD4 <2000cells/µl). E • CT brain findings – edema, ring-lesion, nodular lesion, leptomeningeal enhancement, atrophy. F• Associated opportunistic or co-infection: Toxoplasma gondii, Cryptococcus neoformans, CMV, Herpes virus, Hepatitis C and B viruses. (c) mkareem 36
    • 37. Diagram of HIV & its protein locations (c) mkareem 37
    • 38.  HIV-1 Infection is associated with a progressive loss of CD4+ T-cells STAGES OF HIV/AIDS CD4+ T CELL COUNT Early < 500 x 10 000 000/l Late < 200 x 10 000 000/l Advanced < 50 x 10 000 000/l HIV plasma levels during all stages of infection range from just 50 to 11 million virions per ml. The rate of loss of CD4+ T-cells is linked with an increase in viral load. (c) mkareem 38
    • 39. Methodology Sample size calculationSample size was calculated using Power and Samplesoftware Where,P0 = proportion of presence of neurological symptoms inpatient with positive scan = 0.373p1 = proportion of absence of neurological symptoms inpatient with positive CT scan = 0.627α = 0.05 , m=2 , = 80% = 0.8Thus, sample size (n) = 45 powerTo include twenty five percent (25%) drop-out:Number of cases: 45 + 11 = 56Total number of patients needed for the study is =56.Site: In Hospital Raja (c) mkareem I Perempuan Zainab II 39

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