Opportunistic infections Opportunistic infections nDecrease in number of CD4 lymphocytes is condition for development of opportunistic infections n nRisk is started, when number of CD4 lymphocytes drops to number 500 of CD4 lymphocytes/mm3 CD4 count and opportunistic infection TUBERCULOSIS - the most important - the most common OI Epidemiology •One-third of the world´s population is infected with TB •HIV infection has had a big impact in increasing the numbers of patients affected with disease caused by TB •TB is the most important severe opportunistic infection among patients with HIV in developing countries Global_EstimatedTB06_ITH2009 TB – estimated new cases (per 100 000) • Tuberculosis •Is a leading cause of HIV-related deaths worldwide •In some countries with higher HIV preavalence, up to 80% of people with TB test positive for HIV •Globally approximately 30% of HIV infected persons are estimated to have n latent TB infection TBincidence_2009.png • nTB is transmissible to both people u uwith HIV infection uuninfected persons u n can be treated and can be prevented šíření TB.jpg • Clinical Manifestations nMyco TB n nIs highly contagious nLeads to a number of serious medical syndromes affecting, at time, n most of the organ systems TB +.jpg nMyco TB can causes: n 1.Pulmonary disease n tPneumonia tCavitary disease Cavities in the lungs (X-ray of thorax) tbc kaverny.jpeg 2. 2.Extrapulmonary disease §Adenitis („scrofula“) §Otitis media §Laryngitis §Miliary TB §Meningitis §Skeletal TB §Gastrointestinal TB §Renal TB… u scrofula scrofula TB.jpg TB absces in brain a13f01a.gif Skeletal TB - destruction of the lumbar vertebrae - skeleton of the Great Moravian Empire tb pateře z velkomoravské říše.jpg Mycobacterium tuberculosis bacteria (G+) is acid-fast, appearing red on a Ziehl-Neelsen stain TBC-Ziel-Nilsen.jpg Primary prophylaxis • conditions pathogen drug CD4+ any + TB exposure (when HIV+ individual is in exposure of TB we must start primary prophylaxis) M. tuberculosis isoniazid (+pyridoxin), rifampicin, pyrazinamid, ethambutol • •Myco TB is highly contagious !!! • n nPneumocystis carinii jiroveci nInfection Pneumocystis carinii jiroveci nIs an opportunistic pathogen, n the natural habitant of which is the lung n nThe organism is an important cause n of pneumonia in the compromised host n nThe organism can be found in other organs and tissues n CD4 count and opportunistic infection • • • sken1 CD4+ lymphocytes depletion – gradual loss of number of CD4 cells CD4+ count •primary HIV infection •asymptomatic infection •early symptomatic infection •late symptomatic infection •final stadium •years •A1 •B2 •C3 Pneumocystis carinii jiroveci nHas a worldwide distribution n nSerologic serveys indicate that already most healthy children have been esposed to the organism n nIt means that we meet with this organism in early childhood n nTaxonomy – the fungal kingdom Incidence nPCP accounted for 42% of all AIDS-indicator diseases before ART n nIncidence of PCP in this population is declining (with ART and prophylaxis) n nBut incidence of extrapulmonary Pn. carinii jiroveci is increasing Extrapulmonary Pn.carinii jiroveci infection ninvolves in fewer than 3% of cases. nLymph nodes (in up to 50% of cases) nSpleen nLiver nBone marrow nGI and genitourinary tracts nAdrenal and thyroid glands nHeart, pancreas, eyes, ears, skin… Incubation Period n n nOn the basis of animal studies, the incubation period is thought to be n n from 4 to 8 weeks Typical Symptoms §Patients with PCP usually develop the following: § § Dyspnea § Mild fever § Nonproductive cough The late signs nPhysical findings of PCP n include the following: § Tachypnea § Tachycardia § Cyanosis t nLung auscultation is usually unremarkable Differential Diagnosis n nThe differential diagnosis of PCP nis very broad and includes § infectious diseases n nand also can mimic § noninfectious diseases Laboratory n nThere is no reliable way to cultivate n the organism in vitro n nA definitive is made by histopathologic n staining, which selectively stain n the wall of Pn. carinii jiroveci, n cysts or nuclei n nPCR technique which demonstrate nuclei acid Cysts of Pn. carinii jir. Methenamine silver stain. In smear from bronchoalveolar lavage. Pn. carinii – trophozoites (growth stage), Giemsa-stained PHIL_2686_PCP.jpg Pn.carinii jiroveci – immunofluorescence with monoclonal antibodies is more sensitive than traditional staining Laboratory nLDH nElevated serum concentrations of lactate dehydrogenase have been reported but are not specific to Pn. Carinii infection nLeucocytes nThe white blood cell count is low nOxygen saturation is very low nIs probably the most sensitive noninvasive test for dg. PCP n nArterial blood gases n demonstrated n §Hypoxia §An increased u alveolar-arterial oxygen gradient n n G:\2000-2012 TVORBA\2009 tvorba\PCP.jpg •Alveolocapillary membrane -characteristic exudate • is in the inter alveolar space Imaging nThe classic findings on chest radiography consist of bilateral diffuse infiltrates involving the perihilar regions. n nAtypical manifestations also have been reported. n nEarly in the course of pneumocystosis, the chest radiograph may be normal. Imaging – HR CT n nThe most important imaging method shows n nWhite glass picture HRCT PCP a nekrozy.jpg •CT -White glass picture Diagnostic/testing procedures nFiberoptic bronchoscopy nWith bronchoalveolar lavage remains the mainstay of Pn. Carinii diagnosis nSputum nis a simple, noninvasive technique, but its sensitivity has extremely low nTransbronchial biopsy and open lung biopsy nare the most invasive, are reserved for situations in which a diagnosis cannot be made by lavage n n n Main treatment nTrimethoprim-sulfamethoxazol n nIs the drug of the first choice for all forms of Pn. Carinii infection n nIt is administered intravenously (orally) at a dosage 120 mg of TSX/kg/d in four divide doses nGlucocorticoids n nAdministration of glucocorticoids to HIV-infected patients with moderate to severe pneumocystosis can improve the rate of survival nThe recommended regimen: n 40 mg prednisone PO twice daily, n with tapering to a dose of 20 mg/d n over a 3-week period Duration of treatment nnon-HIV-infected patients nTreatment of pneumocystosis should be continued for 14 days (better 21 days) n nHIV-infected patients nTreatment of pneumocystosis should be continued for 21 days n Alternative treatment nPentamidine n 4 mg/kg/d by slow intravenous infusion nClindamycin nPrimaquine n avoided in patients with glucose-6- n phosphate dehydrogenase deficiency nTrimethoprim + dapson nAtovaquone n Complications nIn the typical case of untreated PCP, n progressive respiratory compromise n leads to death. n nTherapy is most effective when instituted n early in the course of the disease, before n there is extensive alveolar damage. n Primary prophylaxis n nIs indicated for HIV-infected patients at high risk of developing pneumocystosis n n CD4+ lymphocyte count < 200/mm3 Secondary prophylaxis n nIs indicated for all patients nwho have recovered from PCP nProphylactic regimen nTrimethoprim-sulfamethoxazol n (160mg of trimethoprim) per day n nAlternative regimens nDapsone (50mg daily), pyrimethamine (50mg once per week), and folinic acid (24mg once per week) nDapsone (100mg daily) nNebulized pentamidine n (300mg once per month via nebulizer) Primary prophylaxis • conditions pathogen drug CD4+ any + TB exposure M. tuberculosis isoniazid (+pyridoxin), rifampicin, pyrazinamid, ethambutol CD4+ < 200/mm3 Pn. carinii jiroveci co-trimoxazol, pentamidine (aerosol), dapson • n nTOXOPLASMOSIS DEFINITION •An acute or chronic infection caused n by the obligate intracellular protozoan n Toxoplasma gongii n •Infection in human is usually asymptomatic n •When symptoms occur, n they range from a mild, self-limited n to a fulminant disseminated disease SYMPTOMS nUsually involve the following: •Central nervous system •Eyes •Skeletal or cardiac muscles •Lymph nodes •Liver •Lungs DISEMINATED DISEASE nSevere infections usually occur n •In an immunocompromised patient n •By the transplacental passage of parasites n from an infected mother to the fetus n (congenital toxoplasmosis) toxo.jpg bradyzoit-cysta ve tkáni.jpg •Cysts in tissue EPIDEMIOLOGY nCases are caused by: •Eating undercooked meat •Contaminated vegetables •Ingestion of oocysts u from contaminated soil nThe seroprevalence depends on geografic location: US – between 3-67% n tropical countries – up to 90% SYMPTOMS AND SIGNS •Immune responses are able to eliminate most of the tachyzoites • •80 – 90% of cases in immunocompetent persons are asymptomatic CEREBRAL TOXO nClinical manifestations of CNS infection include the following: •Headache, seizures,weakness •Cranial nerve abnormalities •Visual field defects •Mental status changes •Cerebellar signs t CEREBRAL TOXO •Speech abnormalities •Meningism •Sensory or motor disorders •Disorientation •Hemiparesis •Convulsions •Coma and death EXTRACEREBRAL TOXO •Less common among patients with HIV inf. •The prevalence is estimated n at 1,5% to 2,0% •lungs (pneumonitis) •eye (chorioretinitis) •heart nCases of gastrointestinal, liver, skin, or multiorgan involvement also have been reported IMAGING nOn neuroimaging (CT, MRI) nThe abscesses of cerebral toxoplasmosis are typically •Multiple •Located in the cortex or deep nuclei (thalamus and basal ganglia) •Surrounded by edema •Enhance in a ringlike pattern with contrast 26 •Cerebral toxoplasmosis toxo absces 2.jpg SEROLOGY •Approx. 20% of patients n have no detectable antibodies •Titer of antibodies does not always rise during infection •Negative serology does not rule out infection •But a rising titer may be of diagnostic significance OTHER LABORATORY METHODS nPCR (polymerase chain reaction) n in blood samples suggest that •This modality has limited diagnostic value in cases of cerebral toxoplasmosis n nCSF (cerebrospinal fluid) •Is also nonpathognomonic and reveals elevated protein and mild pleocytosis • nEXTRACEREBRAL TOXOPLASMOSIS •Involving other organs among HIV-infected patients is rare •Dg. is usually based on biopsy n nOCULAR TOXOPLASMOSIS •Is usually based on a suggestive ophthalmoscopic picture •Histopathologic identification of T.gondii n in the eye can establish the diagnosis retinochoroiditis Severe,_active_retinochoroiditis_by_Toxoplasma_gondii.jpg MAIN TREATMENT nThe regimen of choice for acute therapy •Pyrimethamine 50 to 75 mg/d n + sulfadiazine 4 to 8 g/d •Leucovorin – coadministtered to prevent the folinic acid deficiency and ameliorate the hematologic toxicity of pyrimethamine •Duration of treatment n – usually for 6 to 8 weeks PATIENT FOLLOW-UP nAfter induction treatmen •HIV-infected patients schould receive lifelong suppression therapy n pyrimethamine 25-50 mg/d n + sulfadiazine 2-4 g/d •The doses of TMP/SMX recommended for P. carinii pneumonia appear to be effective PREVENTION FOR INDIVIDUALS AT RISK • •Not to eat raw or undercooked („pink“) meat •Wash fruits and vegetables •Wash hands after contact with raw meat n and after contact with soil •Wash hands after changing a cat litter box PRIMARY PROPHYLAXIS • conditions pathogen drug CD4+ any + TB exposure M. tuberculosis isoniazid (+pyridoxin), rifampicin, pyrazinamid, ethambutol CD4+ < 200/mm3 Pn. carinii jiroveci co-trimoxazol, pentamidine (aerosol), dapson CD4+ < 150/mm3 + antibody to Toxoplasma positive Toxoplasma gondii co-trimoxazol, dapson, pyrimethamin(+folinat) CONGENITAL TOXOPLASMOSIS •Clinical findings are variable •There may be no sequelae, or sequelae may develop at various times after birth •Premature infants may present with CNS or ocular disease •Full-term infants usually develop milder disease, with hepatosplenomegaly and lyfadenopathy CONGENITAL TOXOPLASMOSIS nSabin tetrade (classic tetrade of signs) 1. 1.Retinochoroiditis 2.Hydrocephalus 3.Convulsions 4.Intracerebral calcifications