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Home , Anal dysplasia, Candidiasis, Coccidioidomycosis, Microsporidiosis, Thrombocytopenic purpura

ACRN Review Course

Recognizing Common Opportunistic Infections

Presented By: Stephen Perez, PhD, RN, CRN Infection Preventionist Hospital of the University of Pennsylvania Today’s Discussion

• What defines an (OI)? • Why do OIs still matter? • Case-based discussion – Recognition (symptoms) – Treatment (medical management) – Prevention (prophylaxis)

MidAtlantic AETC DO OPPORTUNISTIC INFECTIONS STILL MATTER? Opportunistic Infections

• Infections that are more frequent or more severe because of immunosuppression in persons living with HIV • Early 1990s, chemoprophylaxis, immunizations, and improved management of acute OIs  improved survival • Mid-1990s in the ART era  ability to reduce OI-related mortality & improved quality of life

Centers for Disease Control and Prevention. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. MMWR 2009; 58(No. RR-4).

MidAtlantic AETC Correlation of Complication with CD4 cell Counts

>500/mm3 <200/mm3 • Acute retroviral syndrome • Pneumocystis ‡ • Candidal • Disseminated and • Persistent generalized (PGL) • Miliary/extrapulmonary TB • Progressive multifocal leuko - • Guillain-Barré syndrome encephalopathy (PML) • Myopathy • Wasting • Aseptic • Peripheral neuropathy 200-500/mm3 • HIV-associated dementia • Pneumococcal and other bacterial pneumonia • Cardiomyopathy • Pulmonary • Vacuolar myelopathy • Herpes zoster • Progressive polyradiculopathy • Non-Hodgkin’s lymphoma • Oropharyngeal (thrush) <100/mm3 • Cryptosporidiosis, self-limited • Disseminated • Kaposi’s sarcoma • Toxoplasmosis • Oral hairy • • Cervical and anal dysplasia • Cryptosporidiosis, chronic • Cervical and anal • • B-cell lymphoma • Candidal • Anemia <50/mm3 • Disseminated cytomegalovirus (CMV) • Mononeuronal multiplex • Disseminated Mycobacterium avium complex • Idiopathic thrombocytopenic • Primary central nervous system lymphoma (PCNSL) • Hodgkin’s lymphoma • * Most complications occur with increasing frequency at • Lymphocytic interstitial pneumonitis lower CD4 cell counts.

Correlation of Complications With CD4 Cell Counts (see Arch Intern Med 1995;155:1537)

MidAtlantic AETC Correlation of Complications with CD4 cell Counts

>500/mm3 • Acute retroviral syndrome <200/mm3 • Candidal vaginitis • Pneumocystis pneumonia ‡ • Persistent generalized lymphadenopathy (PGL) • Disseminated histoplasmosis and coccidioidomycosis • Guillain-Barré syndrome • Miliary/extrapulmonary TB • Myopathy • Progressive multifocal leuko - • encephalopathy (PML) 200-500/mm3 • Wasting • Peripheral neuropathy • Pneumococcal and other bacterial pneumonia • HIV-associated dementia • Pulmonary tuberculosis • Cardiomyopathy • Herpes zoster • Vacuolar myelopathy • Oropharyngeal candidiasis (thrush) • Progressive polyradiculopathy • Cryptosporidiosis, self-limited • Non-Hodgkin’s lymphoma • Kaposi’s sarcoma <100/mm3 • Oral hairy leukoplakia • Disseminated herpes simplex • Cervical and anal dysplasia • Toxoplasmosis • Cryptococcosis • Cervical and • Cryptosporidiosis, chronic • B-cell lymphoma • Microsporidiosis • Anemia • Candidal esophagitis • Mononeuronal multiplex <50/mm3 • Idiopathic thrombocytopenic purpura • Disseminated (CMV) • Hodgkin’s lymphoma • Disseminated Mycobacterium avium complex • Lymphocytic interstitial pneumonitis • Primary central nervous system lymphoma (PCNSL) • * Most complications occur with increasing frequency at lower CD4 cell counts.

Correlation of Complications With CD4 Cell Counts (see Arch Intern Med 1995;155:1537)

MidAtlantic AETC PREVENTING OPPORTUNISTIC INFECTIONS How to Prevent Opportunistic Infections (OIs)

• Diagnose HIV Infection • Individuals unaware of HIV status may not seek care until present with OI • Treat HIV Infection • Increasing CD4 > 200 to decrease risk of OIs • Prophylaxis • Decreases risk of OIs

MidAtlantic AETC Primary and Secondary Prophylaxis for Opportunistic Infections

• Primary prophylaxis--treatment given to HIV infected individuals to prevent a first episode of an OI • Secondary prophylaxis or maintenance therapy--treatment given to HIV-infected individuals to prevent a recurrence of the infection • Primary prophylaxis is recommended to prevent 3 important OIs: Pneumocystis jiroveci pneumonia (PCP), Mycobacterium avium complex (MAC), and toxoplasmosis.

MidAtlantic AETC Prophylaxis against Opportunistic Infections

• PCP – CD4 < 200 – TMP/SMX, Dapsone, Pentamidine, Atovaquone

• Toxoplasmosis – CD4 < 100 – TMP/SMX, Dapsone/pyrimethamine, Atovaquone

• Tuberculosis – INH

• MAC – CD4 < 50 – Clarithromycin or Azithromycin

MidAtlantic AETC Prevention

• Avoid—Contact and Exposure • HRSA/HAB Clinical Guide: Preventing Exposure to Opportunistic and Other Infections • Sources of Infection: – Water – Food – Environmental – Respiratory – Bodily Contact – Sexual Contact – IDU – Other Bloodborne – Pets and Animals – Children – Travel

HRSA/HAB Guide for HIV Clinical Care, 2014

MidAtlantic AETC Prophylaxis Summary Fungal Agents

Prophylaxis Infection Primary Secondary D/C 2o Restart 2o No Severe/ ? - frequent Histoplasma No* Yes No - Cryptococcus No Yes Yes** CD4 <100 Coccidiodes No Yes No -

* Consider if CD4 <100 + endemic area (>10 cases/100 pts-yrs) ** CD4 > 100-200 x 6 mo + complete initial therapy + asymptomatic Comparison of Indications to Discontinue Primary & Secondary Prophylaxis

Agent Recommendation o PCP 1 CD4 > 200 for 3 months o 2 CD4 > 200 for 3 months o Toxo. 1 CD4 > 200 for 3 months o 2 CD4 > 200 for 6 months & initial Rx & asymptomatic o MAC 1 CD4 > 100 for 3 months o 2 CD4 > 100 for 6 mos & 12 mos Rx & asymptomatic Diseases Treated with HAART

• • HIV nephropathy (Chemlal et al 2000) • PML (Guidici et al 2000, DeLuca et al 2000) • microsporidiosis (Carr et al 1998) • cryptosporidiosis (Carr et al 1998) • peripheral neuropathy (Martin et al 1999) • Kaposi’s Sarcoma (Wilkinson et al, Tam et al, Hoffmann et al 2000) • HIV encephalopathy (Gendelman et al 1998) PREVENTING EXPOSURES Preventing Exposure

• Barrier precautions to prevent STD’s • Avoid: – Uncooked eggs – Undercooked/raw meats – Unpasteurized milk, soft cheeses – Untreated water, untested well water • Hand washing and personal hygiene

MidAtlantic AETC Preventing Exposure

• Pets – New pets: puppies > 6 months, cats > 1 year – Cats - change litter daily, avoid bites/scratches, flea control – Avoid contact with reptiles – Gloves to clean aquarium - M. marinum

MidAtlantic AETC Preventing Exposure

• Travel - by all means do, but plan ahead • Bottled water • Thoroughly cooked foods • Peel fresh fruits/vegetables • Seek expert travel advice - “know before you go” - Vector avoidance, malaria prophylaxis, endemic fungi, no live virus • http://www.cdc.gov/travel/

MidAtlantic AETC RECOGNIZING OPPORTINISTIC INFECTIONS General Approach to OIs

Remember OLDCARTS? Where do I start? • Evaluate Chronicity • CD4 count • Focal symptoms or Systemic? – Confers risk, but not an absolute (where?) – CD4 Nadir • How long do these symptoms last? • History Worsening? – Previous OIs, PMHx, exposure risks, travel history, other infections • Symptomology: pain? SOB? • Physical Exam Weakness? RESPIRATORY/PULMONARY OPPORTUNITSTIC INFECTIONS RESPIRATORY SYMPTOMOLOGY HIV related Pulmonary Infections

• Bacterial pneumonia • PCP – Acute onset – Gradual onset (wks-mos) – Productive cough – Progressively increased shortness of • Unless early breath – High – Scant cough – Patient feels very sick – Lower fever – Any CD4 count – CD4 usually < 200 – High WBC count • TB – Gradual onset (days-mos) – Productive/dry cough – Fever – Any CD4 but ↑ risk with ↓ CD4

MidAtlantic AETC Diagnosis of Pneumocystis jiroveci Pneumonia

• History – Gradual onset, progressively increasing – Scant cough – Lower fever • Labs – Pulse oximeter reading, especially while walking – CXR • No infiltrates in up to 10 to 20% of cases (early disease) • Usually diffuse, bilateral interstitial pattern, • Cavities, nodules, pneumothorax and blebs may be seen. – High LDH sensitive but not specific – PCP or silver stain if available PCP: Treatment

• Duration: 21 days for all treatment regimens • Preferred: TMP-SMX is treatment of choice – Moderate-severe PCP • TMP-SMX: 15-20 mg/kg/day TMP and 75-100 mg/kg/day SMX IV or PO in divided doses Q6-8H – Mild-moderate PCP • As above, or TMP-SMX DS 2 tablets TID – Adjust dosage for renal insufficiency

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MidAtlantic AETC 25 PCP: Treatment

• Alternatives – Mild-moderate PCP • Dapsone 100 mg PO QD + TMP 15 mg/kg/day PO in divided doses TID – Similar efficacy, fewer side effects than TMP-SMX, but more pills • Primaquine 30 mg (base) PO QD + clindamycin 300 mg PO Q6H or 450 mg PO Q8H • Atovaquone 750 mg PO BID – Less effective than TMP-SMX, but fewer side effects

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MidAtlantic AETC 26 Mycobactermium tuberculosis (Mtb)

MidAtlantic AETC TB-HIV

• 1/3 of the HIV-infected population • TB and HIV mutually affect each co-infected with TB other – 50% of HIV patients in SubSaharan • Active TB accelerates HIV Africa co-infected progression • Up to 70% of smear + TB patients • HIV+ patients recently infected have HIV with TB can progress to active TB • Rates of TB are declining with at rate as high as 37% in first 6 about 3.0 new cases of TB disease months instead of 2 to 5% in 2 per 100,000. years

MidAtlantic AETC

TB and HIV

• As CD4 decreases, extrapulmonary manifestations increase. • CD4 > 300: extrapulmonary TB in up to 28% • CD4 <100: extrapulmonary TB in up to 70% • Sputum smears negative in about 45% of HIV+ patients, but only 25% of HIV- patients • Heavy positivity (3+) seen more frequently in HIV- patients

Tubercle Lung Dis 1993: 75: 191-4

MidAtlantic AETC MTB: Epidemiology (2)

• Infection via inhalation of droplet nuclei with MTB organisms • Latent TB infection (LTBI): usually limits multiplication of TB bacilli, but bacilli may persist – Persons with LTBI are asymptomatic and are not infectious • Active TB disease: can develop immediately after infection (primary TB) or with reactivation of LTBI

May 2013

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MidAtlantic AETC 31 MTB: Epidemiology (3)

• Reactivation of latent TB: – More likely in HIV-infected patients; risk increases soon after HIV infection – 3-16% annual risk in HIV-infected patients; in HIV uninfected, ~5% lifetime risk • TB disease can occur at any CD4 count, but risk increases with progression of • TB coinfection increases HIV viral loads and progression of HIV

May 2013

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MidAtlantic AETC 32 MTB: Preventing Exposure

• HIV-infected patients who travel or work in high- prevalence settings should be counseled about TB infection risk and tested for LTBI • Exposure risks in some health care and correctional settings in the – usual precautions

May 2013

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MidAtlantic AETC 33 MTB: Preventing Disease

• Diagnosis and treatment of LTBI is key aspect of preventing active TB • Treatment of LTBI lowers risk of TB disease (by 62%) and death (by 26%)

May 2013

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MidAtlantic AETC 34 TB Disease: Clinical Manifestations

• Common symptoms included cough, fever, sweats, weight loss, • May be subclinical or have few symptoms, even if culture positive • Immune reconstitution following ART initiation can unmask subclinical TB, with inflammatory reactions at site of infection

May 2013

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MidAtlantic AETC 35 TB Disease: Clinical Manifestations (2)

• Degree of immunosuppression influences clinical, radiographic, and histopathologic presentation of active TB • CD4 count >350 cells/µL: as in HIV uninfected – TB usually limited to lungs – Chest X ray: upper lobe infiltrates, +/− cavitation • Extrapulmonary disease (pleuritis, pericarditis, meningitis, lymphadenitis), more common in HIV infection, regardless of CD4 count – More common in advanced immunosuppression

May 2013

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MidAtlantic AETC 36 TB Disease: Clinical Manifestations (3)

• Advanced HIV – TB may be : high , rapid progression, syndrome – Extrapulmonary TB, with or without pulmonary disease, in most TB patients with CD4 count <200 cells/µL – TB may be subclinical or with few symptoms – Chest X ray: lower lobe, middle lobe, interstitial, and miliary infiltrates are common; cavitation less common • Intrathoracic lymphadenopathy is common – may be poorly formed or absent – Sputum smear and culture may be positive even with normal chest X ray May 2013

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MidAtlantic AETC 37 TB Disease: Diagnosis • Test all for LTBI at time of HIV diagnosis (regardless of TB risks) – If CD4 count <200 cells/µL and no indications for empiric LTBI treatment, retest for LTBI when count rises to ≥200 cells/µL on ART • Annual testing only for those at high risk or repeated or ongoing exposure to active TB

May 2013

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MidAtlantic AETC 38 TB Disease: Diagnosis (4)

TST or IGRA test results • If negative and CD4 count <200 cells/µL: retest after ART initiation and increase in CD4 count to >200 cells/µL • If positive test: chest X ray and clinical evaluation to screen for active TB

May 2013

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MidAtlantic AETC 39 OROPHARYNGEAL OPPORTUNITSTIC INFECTIONS Candidiasis

Oropharyngeal Esophageal • White patches, usually able to be • Difficulty or pain with swallowing scraped • Feel like food is “sticking” after • By be reddened or bleed if being swallowed unroofed • Often experience wt. loss and or • May present with more subtle appetite issues reddened patches (erythematous • Often will have oral thrush also candidiasis) • May or may not be painful • Typically irritated by foods or drinks • Unusual taste Oropharyngeal Candidiasis

MidAtlantic AETC Candida Esophagitis

MidAtlantic AETC Mucocutaneous Candidiasis: Diagnosis

• Oropharyngeal: – Usually clinical diagnosis – For laboratory confirmation: KOH preparation; culture • Esophageal: – Empiric diagnosis: symptoms and response to trial of therapy (usually appropriate before ); visualization of lesions + fungal smear or brushings – Endoscopy with histopathology and culture

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MidAtlantic AETC 44 Additional Oropharyngeal OIs

Oral Hairy Leukoplakia Oral Ulcerations Can be affected by CD4 count • Typically seen in CD4 counts <200 • Multiple etiologies • Caused by EBV • – Aphthous Ulcers • Typically on lateral sides of tongue or – Viral (HSV, CMV) buccal mucosa – Bacterial • Cannot be wiped off • • Can appear flat or “hairy” – Neoplasm • Can be large or small • Conservative treatment or topical • Not painful treatment should be followed closey until resolution • Responds to ART Additional Oropharyngeal OIs

Oral Hairy Leukoplakia Oral Ulcers OPHTHALMIC OPPORTUNISTIC INFECTIONS SYMPTOMOLOGY: Vision Loss/Impairment • Obtain history • Differential: – Acute vs gradual – Infection – Blurring, floaters • CMV, HSV, VZV – Photosensitivity, flashes • IRIS – Acuity vs color – Trauma/Foreign body – Visual field loss – Malignancy – Pain, redness, dryness, discharge, • KS, lymphoma swelling – Optic Neuritis – Falls/injuries – Stroke – Other symptoms – Glaucoma • Put in context of medical history • Need Opthalmologic – CD4, ART, etc. Exam/Evaluation

MidAtlantic AETC CMV

• Also could have had no symptoms, decreased vision, scotomata, visual field defects • Differential diagnosis HIV retinopathy, Herpes Zoster (PORN), bacteria, , and toxoplasmosis • Distinguish by exam • Usually presents unilaterally • CD4 < 50 • Vision loss often irreversible Other Manifestations of CMV

• • Pneumonitis • Second most common clinical • Uncommon • Shortness of breath, dyspnea on exertion, manifestation of CMV nonproductive cough, hypoxemia • 5-10% of persons with CMV • CXR: interstitial infiltrates end-organ disease • Encephalitis • more acute course; cranial nerve palsies, • Fever, weight loss, anorexia, abdominal nystagmus, other focal neurologic signs, rapid pain, severe , malaise progression to death • Mucosal hemorrhage and perforation; • CT or MRI: periventricular enhancement can be life threatening • Radiculitis • Esophagitis • Urinary retention, progressive bilateral leg weakness; progresses over weeks to loss of • Occurs in <5-10% of persons with CMV end- bowel and bladder control, flaccid paraplegia organ disease • Spastic myelopathy, sacral paresthesia • Fever, , , mid-epigastric possible or retrosternal discomfort • CSF: neutrophilic pleocytosis, low glucose, elevated protein

MidAtlantic AETC CNS OPPORTUNISTIC INFECTIONS Opportunistic CNS Diseases Any CD4 CD4 < 50-100 • Mycobacterium tuberculosis • Cryptococcus neoformans • Nocardia • Herpesviruses (VZV, HSV, HHV-8) • Toxoplasma gondii • Treponema Pallidum • Progressive multifocal • Many of these occur at increased leukoencephalopathy (PML) - JC frequency as CD4 declines virus • Primary CNS lymphoma (EBV) • CMV • HIV dementia, encephalitis

MidAtlantic AETC CNS OI SYMPTOMOLOGY

Focal Neurologic Deficits Non-focal findings • Hemiparesis • • Cranial Nerve abnormalities • Dizziness • Speech abnormalities • Fever (not always) • Unsteady gait • Lethargy • Vision loss • Confusion • Seizure • Memory/personality changes CNS Toxoplasmosis

MidAtlantic AETC Toxoplasma gondii

• Seropositivity can be as high as 70% • Symptoms – Focal neurologic deficits (hemiparesis, • Most frequent cause of focal CNS speech abnormalities, cranial nerve lesions in patients with AIDS deficits), seizure – CNS disease occurs in 3-10% of – Fever, headache, lethargy AIDS cases – May progress to coma if untreated • Diagnosis – 30% of seropositive patients – Toxo IgG + in 90% develop CNS disease without – Ring enhancing lesion on CT scan prophylaxis • If no CT: treat for Toxo. • Less likely in Toxo IgG - patients and • If no response in 1-2 weeks, consider patients receiving TMP-SMX alternate diagnosis such as CNS lymphoma

MidAtlantic AETC Other Diagnoses • CNS Lymphoma • PML – 2-6 % patients pre-HAART – 1-2% AIDS patients – Focal or nonfocal signs – JC virus causes demyelination – Confusion, headache, aphasia, – Multifocal symptoms: cognitive hemiparesis, and/or seizures impairment, visual field deficits, speech – No fever defects, incoordination, limb weakness, sensory loss – Diagnosis • CT/MRI – Diagnosis by MRI ideally, and isolation – Corpus callosum, Periventricular of virus area, Periependymal area • Hypodense white matter lesions – Usually have mass effect • No edema or enhancement – Often > 4 cm – Only treatment is ART • – Median survival 1-6 months – Without CT scan/MRI treat for Toxo and – Predictor of survival is baseline CD4 consider if no response – Treatment: Radiation, and ART

MidAtlantic AETC Primary CNS Lymphoma

MidAtlantic AETC PML

CT SCAN MRI Cryptococcal Meningitis • Prevalence • Lumbar Puncture – 5-8% in AIDS cases in US • Before widespread ART – elevated opening intracranial – Incidence now much lower pressure, • Symptoms (subacute meningitis – monocytic pleocytosis, or meningoencephalitis) – Fever, headache, nausea/vomiting, – normal-elevated protein, irritability – normal-decreased glucose, – Classic meningeal signs 25-35% • Severe Disease – positive cryptococcal antigen and – cranial nerve palsies, confusion, culture obtundation, seizures – Rarely have focal neurologic – India ink: 60-80% sensitivity deficits – Usually evolves subacutely • Cryptococcal Antigen: 96% sensitivity – CD4 < 50 – If unable to get LP, can check blood Ag

MidAtlantic AETC Other Presentations of

MidAtlantic AETC OI’S COMMONLY MANIFESTING IN SKIN SKIN SYMPTOMOLOGY

Dermatologic Signs Systemic Signs • Lesion • Fever – Pustular • Chills – Macular • (Distribution) – Distribution • Other system involvement (m/s, GI, – Onset Neuro) – Size – Color • Allergy symptoms – Discharge – Scaling – Pain • Puritis EOSINOPHILIC

• Exact cause unknown (inflammatory) • Microbial agent unclear • Possibly Demodex mites • Typically seen below 200 cd4 cells • Very puritic • Very concerning for patients • Can be seen in immune reconstitution HHV-8 Disease: Epidemiology

• Associated with Kaposi sarcoma (KS) (all forms) and certain neoplastic and lymphoproliferative disorders (primary effusion lymphoma [PEL]), multicentric Castleman disease) • HHV-8 seroprevalence in United States: 1-5% – Higher in MSM regardless of HIV serostatus (20-77%) – Higher in some Mediterranean countries (10-20%) and parts of sub- Saharan Africa (30-80%)

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MidAtlantic AETC HHV-8 Disease: Epidemiology (2)

• Pathogenesis of HHV-8 disease is unclear • KS and PEL usually seen in advanced immunosuppression (CD4 count <200 cells/µL), but can occur at any CD4 count • KS incidence up to 30% among AIDS patients in United States before use of effective ART • Dramatically lower incidence in recent years – ART prevents and may regress KS lesions – Ganciclovir, foscarnet, and cidofovir given for CMV treatment may prevent or suppress KS • Castleman disease and PEL remain rare

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MidAtlantic AETC HHV-8 Disease: Clinical Manifestations

• KS presentation varies widely – Most have nontender, purplish, indurated skin lesions – Intraoral lesions are common – Visceral dissemination may occur

Credit: P. Volberding, MD; UCSF Center for HIV Information Image Library

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May 2013 Varicella Zoster • Reactivation of VZV that had been latent in dorsal root ganglia since original infection with VZV () • Can occur at any CD4 count • Prodrome of pain in affected dermatome, then characteristic skin lesions in same dermatome Credit: © I-TECH • Also can present as – Pain often out of proportion to exam – Progressive outer retinal necrosis • CD4 < 50 – Acute retinal necrosis

MidAtlantic AETC VZV Disease: Clinical Manifestations (4)

Herpes zoster (): – Recurrence in 20-30% of HIV infected (same or different dermatome) – Postherpetic neuralgia in 10-15% of HIV-infected persons • Complications more common if CD4 count <200 cells/µL – Neurologic syndromes: CNS , multifocal leukoencephalitis, ventriculitis, myelitis and myeloradiculitis, optic neuritis, cranial nerve palsies, aseptic meningitis

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July 2013 Other with Skin Manifestations

G. Beatty, MD, A. Lukusa, MD, HIV InSite • Bacillary Angiomatosis (Bartenellosis) • • May involve any organ system • Umbilicated lesions • Skin lesions may resemble KS • Low CD4 • (lytic lesions), Peliosis hepatica • Systemic symptoms of fever, sweats, fatigue, malaise, weight loss

MidAtlantic AETC POTPOURRI MYCOBACTERIAL DISEASE Mycobacterium Avium Complex (MAC)

• CD4 < 50, but usually less • Labs than 25 – Cytopenias – Elevated alkaline phosphatase • Not on HAART – Elevated transaminases • Symptoms • Diagnosis – Persistent, high fever – Culture – • Blood culture but takes 7-14 days – GI symptoms • Biopsy liver, lymph node, bone marrow • Diarrhea, abdominal pain • CT of the abdomen will show – Weight loss adenopathy • Disseminated disease

MidAtlantic AETC Immune Reconstitution Syndrome

• As the immune system is IRS is usually seen with: reconstituted with initiation of • ART, an intense inflammatory – MAC, CMV response can be seen in the body. – HSV, VZV – Causes numerous – Pulmonary TB and TB adenitis as immune system reacts to bacteria, viruses or parasites present in the body • Also described with • Occurs a few weeks to months – PCP, after starting ART – Strongyloides • This can also result in diseases – Cryptococcal meningitis occurring at higher than expected CD4 ranges.

MidAtlantic AETC FUNGAL DISEASE Histoplasmosis: Clinical Manifestations • Disseminated disease: fever, fatigue, weight loss, hepatosplenomegaly – Cough, chest pain, dyspnea in 50% – Shock and multiorgan failure in 10% – Most common in patients with low CD4 count • Isolated pulmonary disease: usually occurs in patients with CD4 count >300 cells/µL • CNS, GI, and skin manifestations possible – CNS: fever, headache, seizures, focal neurological deficits, altered mental status – GI: fever, diarrhea, abdominal pain, weight loss

May 2013

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MidAtlantic AETC 75 Histoplasmosis: Clinical Manifestations (2)

Acute disseminated histoplasmosis, chest X ray (L) and CT scan (R)

Credit: Images courtesy AIDS Images Library (www.aids-images.ch)

May 2013 www.aidsetc.org

76 Skin Manifestations

Credit: Image courtesy AIDS Images Library www.aidsimages.ch

MidAtlantic AETC “Opportunistic” Infections in HIV

Pathogens that cause disease in non-HIV infected patients usually occur with a higher incidence in HIV infected individuals

• S pneumoniae • – >150 times more common than in HIV • Campylobacter uninfected – Recurrence in 8-25% within 6 months • Shigella • H influenzae • Syphilis • P aeruginosa • S aureus • Atypicals

MidAtlantic AETC Bacterial Enteric Disease: Epidemiology • Higher incidence of gram-negative enteric infections among HIV-infected patients – Risk greatest if CD4 <200 cells/µL or AIDS – Risk decreased with ART • Most commonly cultured bacteria: • Salmonella • Shigella • Campylobacter • E coli • Clostridium difficile

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MidAtlantic AETC 79 Bacterial Enteric Disease: Epidemiology

• Source usually ingestion of contaminated food or water • Other risks: – Oral-fecal exposure through sexual activity (especially Shigella and Campylobacter) – HIV-related alterations in mucosal immunity or intestinal integrity, gastric acid-blocking

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MidAtlantic AETC 80 Bacterial Enteric Disease: Clinical Manifestations

• Three major clinical syndromes – Self-limited – Diarrheal disease +/- fever, bloody diarrhea, weight loss, possible bacteremia – Bacteremia associated with extraintestinal involvement, with or without GI illness

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MidAtlantic AETC 81 Bacterial Enteric Disease: Clinical Manifestations • Severe diarrhea: ≥6 loose stools per day, with our without other signs/symptoms • In HIV infection: – Greater risk of more serious illness with greater immunosuppression – Relapses may occur after treatment • Recurrent Salmonella bacteremia is an AIDS-defining illness

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MidAtlantic AETC 82 Summary

• Diagnosis and management of OIs is complex – Use guidelines to assist with management – Be alert for more than one infection • Best strategy is to prevent OIs – Diagnose HIV infection earlier – Treat HIV Infection – Provide OI prophylaxis • If initiate ART after treatment of OI, may be able to discontinue prophylaxis once CD4 high enough for > 6 months

MidAtlantic AETC DONE!!

MidAtlantic AETC Thank you

MidAtlantic AETC MidAtlantic AIDS Education and Training Center - Contact Information

Regional Partner: Headquarters: Abby Plusen, MSSW MidAtlantic AIDS Education and University of Maryland Training Center MidAtlantic AIDS Education and Department of Infectious Diseases Training Center and Microbiology, 22 S. Greene Street, Box 175 Graduate School of Public Health, Baltimore, MD 21201 University of Pittsburgh o-410.328.2436 412-624-1895 c-410.960.3262 [email protected] [email protected] www.pamaaetc.org

Linda Rose Frank, PHD, MSN, ACRN, FAAN Principal Investigator and Program Director Associate Professor of Public Health, Medicine & Nursing University of Pittsburgh

MidAtlantic AETC