long-winded: subacute and chronic pulmonary infections · •diagnostic criteria (for mac, m....
TRANSCRIPT
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LONG-WINDED: SUBACUTE AND
CHRONIC PULMONARY INFECTIONS
Elisabeth Merchant, MDChief Resident
Department of MedicineTufts Medical Center
Boston, MA
OBJECTIVES
• List the infections that can present as subacute or chronic dyspnea or cough in an immunocompetent host
• Perform the indicated work-up to diagnose infectious causes of subacute or chronic dyspnea or cough
• Describe the first-line treatments for some of the infectious causes of subacute or chronic dyspnea or cough
• We will NOT be covering:• Acute pulmonary infections• Pulmonary infections in patients with immunocompromised
hosts
DISCLOSURES
• I have no conflicts of interest or financial disclosures related to this presentation.
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CASE 134 year old man with no past medical history presented with 5 weeks of progressive cough, initially productive of clear phlegm and now with blood-tinged sputum.
Differential diagnosisV VascularI InfectiousN Neoplastic/NeurologicD Drugs/toxinsI Inflammatory/Idiopathic
C CongenitalA AutoimmuneT TraumaE Endocrine/MetabolicS pSychologic
CASE 134 year old man with no medical history presented with 5 weeks of progressive cough, initially productive of clear phlegm and now with blood-tinged sputum.He was seen in clinic 2 weeks prior and treated for post-nasal drip, without improvement.Review of symptoms was positive for few pounds of weight loss and occasional chills.He is an “occasional” tobacco smoker and alcohol drinker, but denies use of other drugs. He is from CT, but does travel, most recently to Bermuda 1 year ago.Exam revealed a well-appearing man with normal vital signs and exam (including lungs clear to auscultation).
APPROACH TO INFECTIONS
Viruses
Bacteria
Mycobacteria
Fungi
Parasites
Chronic
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Viruses
Bacteria
Mycobacteria
Fungi
Parasites
VIRUSES
• Viruses are the most common cause of respiratory infections
• Adenovirus, enterovirus, coronavirus, human metapneumovirus, rhinovirus, influenza, parainfluenza, respiratory syncytial virus
• Usually limited to upper airways
• Most viruses have a relatively acute time-course
Troy NM, Bosco A. Respir Res. 2016;17:156.
CHRONIC VIRAL INFECTIONS
• HIV• Pulmonary Arterial Hypertension
• Persons with HIV are several thousand times more likely to develop PAH
• Increased risk for COPD and lung cancer• Thought to be driven by non-HIV risk factors (e.g. smoking)
• Hepatitis C• Chronic infection associated with idiopathic pulmonary
fibrosis• HCV appears to be able to initiate or worsen COPD• Mixed cryoglobinemia leads to vasculitis, pulmonary
hemorrhage• Cirrhosis can also lead to hepatopulmonary syndrome with
pulmonary hypertensionChu C et al. Am Fam Physician. 2017;96(3):161-9., Ilyas SZ, et al. Viral Immunol. 2017;30(9):633-641., Jarret H, Barnett C. Curr Opin HIV AIDS. 2017;12(6):566-571.
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Viruses
Bacteria
Mycobacteria
Fungi
Parasites
BACTERIA
• Pulmonary bacterial infections are also more typically acute, as well as being more severe, in their presentation
• Chronic structural lung diseases (COPD, bronchiectasis, cystic fibrosis) can present with chronic bacterial infection
• H. influenza, Pseudomonas aeruginosa, S. pneumoniae, M. catarrhalis
Parmeswaran GI, Murphy TF. Infect Dis Clinc North Am. 2007;21(3):673-95.
BACK TO CASE 1
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Sputum cultures with mycoplasma chelonae
EM1
Viruses
Bacteria
Mycobacteria
Fungi
Parasites
MYCOBACTERIA• “Myco” is Greek for fungus – felt to appear mold-like on
culture
• Acid fast, aerobic, bacilli
• Unique cell wall – thicker than other bacteria, hydrophobic,
• Naturally resistant to many antibiotics that disrupt cell-wall biosynthesis (like Penicillin)
• Can survive long exposures to many exposures including acids, alkalis, detergents, and complement
• Neither gram positive nor negative, some characteristics of both
Trifiro S, et al. J Clin Microbiol. 1990;28(1):146-7.
Slide 13
EM1 Elise Merchant, 1/29/2019
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NON-TUBERCULOUS MYCOBACTERIA (NTM) REFERS TO MYCOBACTERIA OTHER THAN M. TUBERCULOSIS AND M.
LEPRAE
• Usually acquired by inhalation or ingestion• No documented cases of person-to-person
transmission
• Ubiquitous in the environment, including household water, natural water sources, and soil
• Resistant to commonly used water disinfectants (e.g. chlorine)
• Recent study (Gebert et al., 2018) found regional association between pathogenic NTM in showerheads and clinical NTM infections
Gebert MJ, et al. Mbio. 2018;9(5). Pii:e101614-18.https://www.nationaljewish.org/NJH/media/pdf/Is-Your-Shower-Head-Making-You-Sick-Infographic-by-National-Jewish-Health_1.pdf
NTM FOUND IN SHOWERHEAD BIOFILMS
Copyright © 2018 Gebert et al.
Gebert MJ, et al. Mbio. 2018;9(5). Pii:e101614-18.
>200 SPECIES OF NTM…
Correct speciation is important because species have differing clinical relevance:Some are likely pathogens when found in sputumWhile others are likely contaminants
Griffith et al. Am J Respir Crit Care Med. 2007;175(4):367-416., Koh WJ. Microbiol Spectr. 2017;5(1). , Parte AC. Int J Syst Evol Microbiol. 2018;68(6):1825-9.
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IMPORTANT NTM TO KNOW, EVEN IF YOU AREN’T IN
INFECTIOUS DISEASE*:• M. avium Complex
• Most common NTM pulmonary infection• Originally two species, M. avium and M. intracellulare
• Now multiple other species within complex including M. chimaera• Clinical differences and importance of differentiation remains
unclear• M. kansasii
• Considered most virulent NTM• Second most common etiology of NTM in much of Europe
• M. abscessus complex• Important source of pulmonary infections in those with chronic
lung diseases• Divided into subspecies that have different responses to
antibiotics
Koh WJ. Microbiol Spectr. 2017;5(1). Perkins et al. MMWR. 2016;65:1117-8..
*Which must be sad
FOUR CLINICAL SYNDROMES
Koh WJ. Microbiol Spectr. 2017;5(1).
90% of NTM infections involve
the lungs!
Chronic productive coughHemoptysisFatigueMalaiseWeight loss
RISK FACTORS
• Structural Lung Disease• Cystic Fibrosis• Bronchiectasis• Primary ciliary dyskinesia• COPD• Previous TB• Pneumoconiosis
• Immunosuppression• HIV• Transplant• TNF- α inhibitor use• Defects in IL-12/IFN-γ
Chan ED and Iseman MD. Semin Respir Crit Care Med. 2013;34(1);110-23. Koh WJ. Microbiol Spectr. 2017;5(1).
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LADY WINDERMERE SYNDROME
• Immunocompetent, otherwise healthy older women
• Particularly with thin body habitus• Also associated with thoracic cage
abnormalities like scoliosis and pectus excavatum
• ?Marker for underlying genetic predisposition
• Historically thought to be due to cough suppression
• May be related to lower estrogen levels, altered expression of leptin and adiponectin
Chan ED and Iseman MD. Semin Respir Crit Care Med. 2013;34(1);110-23.
“CLASSIC” PRESENTATION –FIBROCAVITARY
• Symptoms and radiographic findings similar to tuberculosis
• Nodules with predilection for apical and posterior segments
• Can develop into cavities• Usually <2.5cm
• Mediastinal lymphadenopathy and pleural effusions are rare
Koh WJ. Microbiol Spectr. 2017;5(1).Parkar and Kandiah. J Belg Soc Radiol. 2016;100(1):100.
“NON-CLASSIC” –NODULAR
BRONCHIECTATIC• Bronchiectatic disease• Centrilobular nodules; tree-in-bud pattern• Cavitation and mediastinal lymphadenopathy are rare
https://openi.nlm.nih.gov/detailedresult.php?img=PMC4823187_trd-79-74-g002&req=4Koh WJ. Microbiol Spectr. 2017;5(1).Parkar and Kandiah. J Belg Soc Radiol. 2016;100(1):100.
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DIAGNOSIS• All patients with suspected NTM should have:
• Chest X-ray• CT if normal CXR• ≥3 sputum samples for AFB
• Diagnostic criteria (for MAC, M. kansasii and M. abscessus)• Clinical
• Pulmonary symptoms• Imaging with fibrocavitary or nodular bronchiectatic disease• Exclusion of other disorders (including TB)
• Microbiologic• Positive cultures from 2 separate expectorate samples• Positive culture from 1 bronchial lavage• Lung biopsy with granulomatous inflammation or AFB AND
positive culture for NTM (biopsy or sputum)
Griffith DE, et al. Am J Respir Crit Care Med. 2007;175(4):367-416.
If NTM is suspected, but criteria is not met, the patient should be followed closely until the diagnosis is established or excluded
LAB TESTING• Acid-fast staining cannot differentiate TB from NTM!
• NAAT tests need to be performed on AFB-smear positive samples
• Drug susceptibility testing - Discrepancies between in vitro susceptibilities and in vivo outcomes
Koh WJ. Microbiol Spectr. 2017;5(1).
TO TREAT OR NOT TO TREAT…
• Individualized decision!• Why not?
• Long-term treatment with multiple antibiotics that have significant toxiciries
• Microbiologic cures can be difficult to achieve• Nodular bronchiectatic disease
• Tends to occur without other comorbidities and progress slowly• May be less utility to treatment
• Cavitary disease• Higher mortality• Usually requires immediate treatment
• Guidelines for treatment, differs based on species/subspecies• Macrolides, rifampin and ethambutol are mainstays of most
regimens• For MAC pulmonary disease, regimen is continued until culture
negative for 1 yearGriffith DE, et al. Am J Respir Crit Care Med. 2007;175(4):367-416.
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CASE 1 CONTINUED
• Symptoms had already started to improve by time M. chelonae grew
• Decision made to not treat• Patient was followed closely in ID clinic and with
periodic CXRs• Repeat CT 1 year later showed only scar at the site of
previous cavitation
MYCOBACTERIUM TUBERCULOSIS
• Transmitted exclusively via cough aerosol
• Necrotizing granulomatous inflammation, usually in the lung (85%), although almost any other organ can be involved
• ~1/3 of the world’s population has been infected
• 12% actually develop disease• Depends on host
immunocompetence• Still among top 10 causes of
death worldwide• Untreated, active tuberculosis
has a mortality of 70%
Dheda, et al. The Lancet. 2016;387(10024):19-25.
DISEASE COURSEBacteria inhaled
Travel to lung peripheryTaken up by macrophages
Infections may be cleared completely
without risk of activation (?10-20%)
Pleural effusion from rupture into pleural space
Can spread via lymphatics to rest of body
Granulomas formReduced oxygen in center
causes caseation, slows bacterial growth
Can have clinical manifestations, from minor
disease to fulminant infection
Latent TB maintained by continued sequestration by the immune system
Insults to immune system increase risk of
reactivation
Dheda, et al. The Lancet. 2016;387(10024):19-25. Lyon SM, Rossmai MD. Microbiol Spectrium. 2017;5(1):TNMI7-0032-2016.
*
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DIAGNOSIS OF LATENT TB INFECTION (LTBI)
• Interferon-γ release assay (IGRA) recommended in people >5• Likely to be infected with TB
• Household contacts or recent exposure to active TB• Mycobateriology lab personnel• Immigrants from high burden countries• Residents and employees of high risk congregate settings
• Tuberculin skin test (PPD) is an acceptable alternative, especially if IGRA unavailable or too costly
• Likelihood of false positive after BCG vaccine (≥ 10 years) ~1%• NTM can also cause false-positives (0.1-2.3%)
• If unlikely to be infected, testing NOT recommended• If required, positive tests should have a confirmatory repeat to
rule out false positive
Dheda, et al. The Lancet. 2016;387(10024):19-25., Farhat, et al. Int J Tuberc Lung Dis. 2006;10(11);1192-1204., Lewinsohn DM, et al. Clin Infect Dis. 2017;64(2):111-5.
CLINICAL PRESENTATION OF ACTIVE TB
• Fever• Often in the afternoon
• Drenching night seats• Weight loss• Malaise/Fatigue• Symptoms related to involved organs
• For lungs:• Cough, +/- hemoptysis• Pleuritic chest pain• Dyspnea (Late feature - usually indicates widespread
involvement of the lung or airway obstruction)
Dheda, et al. The Lancet. 2016;387(10024):19-25., Lyon SM, Rossmai MD. Microbiol Spectrium. 2017;5(1):TNMI7-0032-2016.
IMAGING• Cavities in 50%• Classic teaching:
• Primary TB with lower lobe consolidation, hilar adenopathy
• Reactivation with upper lobe, fibronodular pattern, cavitation
• Growing evidence that there is NO RADIOLOGIC DIFFERENCE between primary and reactivation TB!
• Immunocompetent adults –Cavitary upper lobe lesions with satellite nodules
• Immunocompromised or children – Lower lung disease, adenopathy, pleural effusions
Lyon SM, Rossmai MD. Microbiol Spectrium. 2017;5(1):TNMI7-0032-2016., Rozenshtein A, et al. AJR. 2015;204(5):974-8
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DIAGNOSIS OF ACTIVE TB• 3 expectorated samples for
• Acid-fast bacilli smear microscopy• Frequent false negatives and false positives
• Mycobacterial cultures
• Nucleic-acid amplification (DNA) testing of ≥ 1 sample• If AFB smear positive, positive NAAT confirms diagnosis• If AFB smear negative but high suspicion, positive NAAT strongly
suggests TB• If negative, test cannot exclude TB alone
• Although with 2 samples sensitivity is 0.95 (CI 0.73-1.0) compared to culture
• If respiratory sample not able to be obtained (or if expectorated sputum negative with high suspicion)
• Sputum induction• Flexible bronchoscopic sampling
Cowan, et al. Clin Infect Dis. 2017 Feb 15;64(4):482-489., Lewinsohn DM, et al. Clin Infect Dis. 2017;64(2):111-5.
LATENT TB TREATMENT
• Reduces risk of tuberculosis development by 70%• Possible regimens:
• Isoniazid daily for 6 or 9 months• Isoniazid and rifampicin daily for 3-4 months• Rifampicin daily for 3-4 months
• Lower hepatotoxicity• Isoniazid and rifapentine weekly for 3 months (DOT)
• Not for children <2• Safe and effective, substantially higher treatment
completion rates• Lower hepatotoxicity
Borisov AS, et al. MMWR. 2018;67(25):723-6., Dheda, et al. The Lancet. 2016;387(10024):19-25., Getahun H, et al. Eur Respir J. 2015;46:1563-76.
TREATMENT OF ACTIVE TB
• RIPE: Isoniazid and rifampicin for 6 months, with pyrazinamide and ethambutol for the first 2 months
• Assumes drug-sensitive (testing should be done first)
• Most serious adverse reaction is liver injury, related to rifampicin, isoniazid, or pyrazinamide (5-33%)
• Repeat sputum smears done at 2 and 5 months
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Viruses
Bacteria
Mycobacteria
Fungi
Parasites
HISTOPLASMA CAPSULATUM
• Found in soil contaminated by bat or bird droppings
• Acute pneumonia few days after substantial exposure (e.g. spelunking)
• Chronic cavitary disease (immunocompetent)
• Frequently associated with emphysema
• Productive cough, dyspnea, weight loss, night sweats, fevers
• Months to years• Disseminated disease
(immunocompromise)• Subclinical exposure can leave small
calcified granulomas in lungs and/or spleen
https://www.cdc.gov/fungal/diseases/histoplasmosis/causes.html
Denning DW, Chakrabarti A. Lancet Infect Dis. 2017;17(11):e357-366., Maiga AW. Emerg Infect Dis. 2018;24(10) :1835-1839., Nett RJ et al. Emerg Infect Dis. 2015;21(6):1071-1072.
Over 1.5 years in 2012-2013, 5 cases in
Montana with no recent (≤ 3 years) travel to endemic
region
COCCIDIOIDES• Asymptomatic in 60%• Primary infection
• Valley Fever - Flu-like symptoms (fever, chest pain, cough, weight loss, erythema nodosom or erythema multiforme)
• Primary pulmonary coccidiomycosis• Nodules or consolidation in lower
lobes• Chronic pulmonary
coccidiomycosis• Persistent cough, weight loss,
malaise• Usually single, thin-walled cavity,
may have multiple nodules or cavities
Denning DW, Chakrabarti A. Lancet Infect Dis. 2017;17(11):e357-366.https://www.cdc.gov/fungal/diseases/coccidioidomycosis/causes.html
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PARACOCCIDIOIDES BRASILIENSIS• Associated with soil where coffee
grows• Immunocompetent and
immunocompromised• Acute presentation
• Patients younger than 30• Adenopathy, unilateral pleural
effusion, miliary-like shadows• Disseminates to other organs• Fatal if untreated
• Chronic pulmonary paracoccidioidiomycosis
• Slowly growing granulomatous nodules that often cavitate
• Often associated with granulomas in other organs (skin/mouth, lymph nodes, spleen, liver, adrenal glands)
Denning DW, Chakrabarti A. Lancet Infect Dis. 2017;17(11):e357-366. Junior MR, et al. Eur J Rad. 2018;103:147-162.
Junior MR, et al. Eur J Rad. 2018;103:147-162.
BLASTOMYCES DERMATITIDIS
• Transmitted via inhalation of soil or bird guano
• Symptom onset in 3 weeks to 4 months• 50% asymptomatic• Most infections in immunocompetent adults• Pulmonary blastomycosis
• Ranges from subclinical to ARDS• Presents with cough, dyspnea, weight loss,
chest pain, fever, and occasional hemoptysis
• Can disseminate (25-40%)• Skin• Bone• Central nervous system• Genitourinary tract
• Can become chronic, with non-specific symptoms (above), and nodules, masses or cavitation on chest x-ray
Denning DW, Chakrabarti A. Lancet Infect Dis. 2017;17(11):e357-366. McBride JA, et al. Clin Chest Med. 2017;38(3):435-449.
https://www.cdc.gov/fungal/diseases/blastomycosis/causes.html
ASPERGILLUS FUMIGATUS
• Ubiquitous• In normal hosts most often causes acute pneumonia
• Can progress to chronic pulmonary aspergillosis• Subacute invasive pulmonary aspergillosis in
immunocompromise• Chronic pulmonary aspergillosis
• 2-10% of cases occur in immunocompetent hosts (mostly with obstructive lung diseases or TB)
• Mostly older males• Progressive over months
• Constitutional symptoms – fatigue, weight loss• Pulmonary symptoms – Cough, hemoptysis, chest
discomfort, dyspnea• Imaging reveals one or more cavities, +/-
aspergilloma, large mass lesions or extensive consolidation
• Pleural thickening is common
Denning DW, Chakrabarti A. Lancet Infect Dis. 2017;17(11):e357-366.
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CASE 2
• A 21 year old man with Lynch Syndrome (predisposition to multiple cancers) is seen in clinic.
• He notes that he has had about 9-10 months of fatigue, decreased exercise tolerance, exertional dyspnea, and occasional left-sided pleuritic chest pain
• As part of his cancer screening, he has an MRCP which shows an incidental large left pleural effusion.
• On further history, he has had significant recent travel.• Singapore, Indonesia and Thaliand 1.5 years ago (hiked,
swam in fresh water and ate raw freshwater crab)• Mexico 2 months ago (ate local foods, but drank bottled
water)
THORACENTESIS
• Exudative fluid• 3921 nucleated cells,
with 52% eosinophils• Gram stain and AFB
smear negative• Flow cytometry
negative for malignant cells
CLINICAL COURSE
• Pigtail placed, but persistent effusion
• Taken to OR for VATS/decortication, which showed necrotic purulent material
• Stool negative for ova or parasites
• Serologies positive for paragonimus
• Improved with Praziquantaltreatment
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Viruses
Bacteria
Mycobacteria
Fungi
Parasites
PARAGONIMIASIS
• Paragonimus (lung fluke)• Ingestion of (undercooked) intermediate hosts (freshwater
crabs, crayfish) in SE Asia, central Africa, or South America• Adult worms found in pulmonary cysts (usually in pairs)
• Can cause pleural effusions or pneumothoraces• Presents with pleuritic chest pain, chronic cough,
hemoptysis, fever• Frequently misdiagnosed as tuberculosis or malignancy
Kunst H, et al.Thorax. 2011;66:528-536.
AMOEBIASIS –ENTAMOEBA HISTOLYTICA
• Protozoa found worldwide• Fecal-oral transmission
• Usually lives in intestinal lumen, causes diarrhea
• Rarely invades mucosa and can form amoebic liver abscess (several months after initial infection)
• Cough from diaphragm irritation• Serous pleural effusion• Atelectasis from right hemidiaphragm elevation
• Amoebic pleuropulmonary disease (trans-diaphragm, hematogenous spread, or lymphatic spread)
• Empyema• Lung abscess• Pneumonia• Hepatobronchial fistula By Stefan Walkowski - Own work, CC BY-SA
3.0, https://commons.wikimedia.org/w/index.php?curid=24557823
Kunst H, et al.Thorax. 2011;66:528-536.
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SCHISTOSOMIASIS• Endemic in tropics• Infection from contact with larvae in
freshwater• Enter circulation, pass through heart, lungs, and
liver before reaching (intrabdominal) veins where they mature and mate
• With heavy infections, migration through the lungs can produce pneumonitis
• Eggs that are not passed in intestines cause chronic disease – granulomas and fibrosis
• Release of eggs results in acute schistosomiasis (Katayama fever) - cough, fever, fatigue
• Pulmonary Hypertension• In severe, chronic infection with S. mansoni and
S. japonicum – hepatosplenomegaly and portal hypertension can divert eggs to lung vasculature, resulting in obliterative arteritis
• Chronic presentation with dyspnea, chest pain, digital clubbing, hypoxemia
http://www.genome.gov/dmd/img.cfm?node=Photos/Animals/Trihinella (NHGRI-79094.jpg,
Kunst H, et al.Thorax. 2011;66:528-536.
HELMINTHS(WORMS)
• Echinococcus (tapeworm) – Hydatid Cysts• Dogs and foxes definitive host, other livestock can be
intermediate• Found in South America, Mediterranean, Middle East, Sub-
Saharan Africa, Russia, and China• Most hydatid cysts form in liver, 20-30% in lungs
• Form over several months to years• Often asymptomatic, can have chest pain, cough, hemoptysis• Cysts rupture can lead to a hypersensitivity reaction with wheezing,
anaphylaxis or pneumothorax• Dirofilariasis immitis (dog heartworm)
• Transmitted from dogs via mosquitos (RARE)• 1-3 cm granulomatous lesion with necrotic center and fibrous
wall• Usually asymptomatic, can have chest pain, cough, hemoptysis,
wheeze, feverKunst H, et al.Thorax. 2011;66:528-536.
TOXOCARIASIS
• Toxocara canis (dog round worm)• Found world-wide in young dogs• Fecal-oral ingestion of eggs (mostly children)• Migrate from intestine to multiple organs• Most infections asymptomatic
• Covert toxocariasis - cough, wheezing, fevers, abdominal pain, headaches
• Visceral Larval Migrans – diffuse inflammation of various organs
• Pulmonary symptoms - cough, asthma, chest tightness• Non-pulmonary symptoms - pallor, fatigue, weight loss, fever,
headache, rash, abdominal pain, nausea, vomiting
By Flukeman - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=3537559
Kunst H, et al.Thorax. 2011;66:528-536.
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TAKE HOME POINTS
• Viral and bacterial infections are more often ACUTE, although both HIV and HCV can have pulmonary complications
• Consider non-tuberculous mycobacteria in a patient with chronic cough and constitutional symptoms, especially if they have immunocompromise or underlying lung disease, or are thin older women
• Consider TB, NTM, and fungi in cavitating lesions• Consider fungal and parasitic infections if history of
travel to endemic region• (Don’t forget to ask!)
REFERENCES• Borisov AS, Bamrah Morris S, Njie GJ, et al. Update of Recommendations for Use of Once-Weekly Isoniazid-Rifapentine
Regimen to Treat Latent Mycobacterium tuberculosis Infection. MMWR Morb Mortal Wkly Rep 2018;67:723–726.• Chu C, Pollock LC, Selwyn PA. HIV-associated complications: A systems-based approach. American Family Physician.
2017;96(3):161-9.• Cowan JF, Chandler AS, Kracen E, Park DR, Wallis CK, Liu E, Song C, Persing DH, Fang FC. Clinical impact and cost-
effectiveness of Xpert MTB/RIF testing in hospitalized pateitns with presumptive pulmonary tuberculosis in the United States.Clinical Infectoius Diseases. 2017 Feb 15;64(4):482-489.
• Denning DW, Chakrabarti A. Pulmonary and sinus fungal diseases in non-immunocompromised patients. Lancet Infect Dis. 2017;17(11):e357-366.
• Dheda PK, Barry CE, M PG. Tuberculosis. The Lancet. 2016;387(10024):19-25.• Farhat M, Greenaway C, Pai M, Menzies D. False-positive tuberculin skin tests: what is the absolute effect of BCG and
non-Tuberculous mycobacteria? International Journal of Tuberculous Lung Disease/ 2006;10(110:1192-1204.• Gebert MJ, Delgado-Baquerizo M, Oliverio AM, Webster TM, Nichols LM, Honda JR, Chan ED, Adjemian J, Dunn RR,
Fierer N. Ecological Analyses of Mycobacteria in Showerhead Biofilms and Their Relevance to Human Health. MBio. 2018;9(5). Pi:e01614-18.
• Getahun H, Matteelli A, Abubakar I et al. Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries. European Respiratory Journal. 2015; 46:1563–76.
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• Ilyas SZ, Tabassum R, Hamed H, Rehman SU, Qadri I. Hepatitis C Virus-Associated Extrahepatic Manifestations in Lung and Heart and Antiviral Therapy-Related Cardiopulmonary Toxicity. Viral Immunology. 2017;30(9):633-41.
• Jarret H, Barnett C. HIV-associated pulmonary hypertension. Current opinion in HIV and AIDS. 2017;12(6):566-571.• Koh WJ. Nontuberculous Mycobacteria – Overview. Microbiol Spectr. 2017;5(1).• Kunst H, Mack D, Banerjee AK, Chiodini P, Grant A. Parasitic infections of the lung: a guide for the respiratory
physician. Thorax. 2011;66:528-536.
MORE REFERENCES• Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL, Daley CL, Desmond E, Keane K, Lewinsohn DA, Loeffler AM,
Mazurek GH, O’Brien RJ, Pai M, Richeldi L, Salfinger M, Shinnick TM, Sterling TR, Warshauer DM, Woods GL. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clinical Infectious Diseases. 2017;64(2):111-5.
• Lyon SM, Rossmai MD. Pulmonary Tuberculosis. Microbiology Spectrium. 2017;5(1):TNMI7-0032-2016.• Maiga AW, Deppen S, Scaffidi B, Baddley J, Aldrich MC, Dittus RS, et al. Mapping Histoplasma capsulatum
Exposure, United States. Emerg Infect Dis. 2018;24(10):1835-1839.• McBride JA, Gauthier GM, Klein BS. Clinical manifestations and treatment of blastomycosis. Clinical Chest
Medicine. 2017;38(3):435-449.• Nett RJ Skillman D, Riek L, Davis B, Blue SR, Sundberg EE, Merriman JR, Hahn CG, Park BJ. Histoplasmosis in Idaho
and Montana, USA, 2012-2013. Emerg Infect Dis. 2015;21(6):1071-1072.• Parameswaran GI, Murphy TF. Infections in Chronic Lung Diseases. Infectious Disease Clinics of North America.
2007;21(3):673-95.• Parkar AP, Kandiah P. Differential Diagnosis of Cavitary Lung Lesions. J Belg Soc Radiol. 2016;100(1).100
• Parte, AC. LPSN – List of Prokaryotic names with Standing in Nomenclature (bacterio.net), 20 years on. International Journal of Systematic and Evolutionary Microbiology. 2018;68(6):1825-1829.
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2/1/2019
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THANK YOU!
• David Stone, MD• Christine Nayar, MD• Laurie Pearson, MD• Will Whalen, MD• Robert Merchant, MD