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Medical journal armed forces india manuscript health and social care essay

Medical Journal Armed Forces India Manuscript DraftManuscript Number: MJAFI-D-13-00091Article Type: Case ReportKeywords: IRIS; Cryptococcus; HAARTAbstract: The immune system recovery in a HIV positive patient who is being treated with HAART leads to a paradoxical increase in immune responses. This is what is known as Immune reconstitution inflammatory syndrome (IRIS). We describe a case of Cryptococcal IRIS in a 39 yr old male who presented with history of short febrile illness, altered sensorium and global headache. Clinically he had fever, altered sensorium, terminal neck stiffness with no localizing signs. Routine hematological and biochemical examination were essentially within normal limits. Urgent CECT brain revealed a normal study. He was found to be reactor for HIV 1. His CD4 count was 12 cells/mm3 and the HIV-1 viral load 428, 714RNA copies/ml. CSF analysis showed a mild increase in cell count (lymphocytes) and protein. CSF culture was sterile. Patient was put on HAART and managed with injectable (Ceftriaxone and Acyclovir) and he showed gradual recovery. On the 6th day of treatment he again had severe headache, fever, vomiting and started behaving abnormally. A repeat CSF analysis showed a further increased cell count and protein and a low sugar level. Culture showed Cryptococcus neoformans growth (susceptible to Amphotericin B). However despite intensive drug regimen, his condition rapidly deteriorated and he succumbed to his illness on 14th day of his admission. IRIS with cryptococcal meningitis is rare and its diagnosis is challenging. Hence confirmation of the disease relies heavily upon case definitions incorporating clinical and laboratory data. It should be suspected in patients who show clinical, radiological or pathological deterioration following initiation of HAARTIntroductionThe HAART for HIV infection has led to significant decline in AIDS-associated morbidity and mortality. These benefits are, in part, a result of partial recovery of the immune system, manifested by increase in CD4+ T-lymphocyte counts and decrease in plasma HIV-1 viral load. However the immune system recovery also leads to a paradoxical inflammatory reaction against a foreign antigen (alive or dead) in patients who have started antiretroviral therapy and who have undergone a reconstitution of their immune responses. This is what is known as Immune restoration disease (IRD) or Immune reconstitution inflammatory syndrome (IRIS). This syndrome has been described in association with various opportunistic pathogens like Mycobacterium avium complex, Mycobacterium tuberculosis, Cryptococcus neoformans, Cytomegalovirus and Hepatitis viruses (1). The incidence of Cryptococcal IRIS varies from 8%–50% of AIDS patients who were started on HAART (2)Case reportA 39 yr old married male presented in the emergency OPD of a tertiary care center with history of short febrile illness, altered sensorium and global headache. Clinically he had fever, altered sensorium, terminal neck stiffness with no localizing signs. Routine hematological and biochemical examination were essentially within normal limits. Urgent CECT brain revealed a normal study. He was found to be reactor for HIV1. His CD4 count was 12 cells/mm3 and the HIV-1 viral load 428, 714 RNA copies/ml. CSF analysis showed a mild increase in cell count (lymphocytes) and protein. CSF culture was sterile. Patient was put on HAART and managed with injectables (Ceftriaxone and Acyclovir) and he showed gradual recovery. On the 6th day of treatment he again had severe headache, fever, vomiting and started behaving abnormally. A repeat CSF analysis showed a further increase in cell count and protein as well as a low sugar level. Culture showed Cryptococcus neoformans growth (susceptible to Amphotericin B). However despite intensive drug regimen, his condition rapidly deteriorated and he succumbed to his illness on 14th day of his admission. DiscussionCryptococcal immune reconstitution inflammatory syndrome (C-IRIS) may present as a clinical deterioration or new presentation of cryptococcal disease following initiation of antiretroviral therapy (ART) and is believed to be caused by recovery of cryptococcusspecific immune responses. A consensus case definition pertaining to this disease entity, has arrived upon two distinct terminologies-a) Paradoxical cryptococcal IRIS in which patients have known cryptococcal disease prior to ART and who subsequently deteriorate while on ART (3) b) ART-associated cryptococcosis where an incident case of cryptococcosis develops during ART (4). A provisional entity of ” unmasking” C-IRIS is also included under this heading. Infection with Cryptococcus neoformans may remain latent for years and is not uncommon to see them re-emerge in severe immunodeficiency, after initiation of ART therapy. Clinically both these forms present in any of the following forms (a) meningitis (2/3 rd cases) (b) space-occupying CNS lesions (c) Necrotic lymphadenopathy (d) Pneumonitis(e) Suppurative soft tissue lesions. Though largely similar, ART associated CM often presents with rapid onset of severe illness over a few days as compared to a sub-acute course typically seen with cryptococcal meningitis (CM) in patients not receiving ART(3)The timing of cryptococcal IRIS after HAART initiation appears to be variable, ranging from less than 1 week to several months (5). Furthermore, most patients who develop IRIS have had high viral loads and very low CD4+ T-lymphocyte (CD4+) counts, as was also seen in our case. Confirmation of a virologic response (reduction in VL of <1 log10) to art is recommended, but not essential, for the diagnosis of c-iris. in our case, due fatal course events, repeat viral load could be done. underlying pathogenesis this disease a marked type-1 cd4 t-helper (th1) response present serum and csf. persons at risk c-iris have scarce inflammation ineffective antigen clearance prior art, followed by presentation on probably deregulated antigen-specific generalized pro-inflammatory (6). central pathogenic role an alteration th1 th2 balance has also been proposed. few studies suggest that elevated c-reactive protein (crp) il-6, 7, 13 concentrations precede development c-iris,compared with art-treated individuals cryptococcosis who do experience iris (7). csf examination remains important investigation work up these cases. relatively higher opening pressure cell count favours over non iriscm. increased pro inflammatory cytokine profiles (e. g. ifn-γ, tnf-α, il-12, il-17) time clinical deterioration, may distinguish from cm-relapse. cryptococcal antigenemia, reflected previous studies, controversial (8). neither positive nor negative>

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