PREVENTING AND TREATING INFECTIOUS DISEASES
Educational Objectives
| The goals of this program are to improve the prevention of infectious diseases by use of established as well as newly
available vaccines and to facilitate diagnosis of less frequently seen respiratory infections. After hearing and assimilating
this program, the clinician will be able to:
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 | 1. List the essential qualities of preventive vaccines.
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| 2. State the latest recommendations for vaccinating health care workers against mumps.
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| 3. Describe the differences (eg, indications, contraindications, side effects) between the injectable and intranasal
influenza vaccines.
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| 4. Discuss the controversies about the human papillomavirus vaccine.
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| 5. Identify atypical presentations of respiratory infections, including psittacosis and nontuberculous mycobacterial
infections.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a
proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.
Acknowledgements
Dr. Winston was recorded at the 36th Annual Advances in Internal Medicine, held May 19-23, 2008, in San Francisco,
CA, and sponsored by the University of California, San Francisco, School of Medicine. Dr. Zenilman spoke at
Third Annual Infectious Diseases Update for the Primary Care Practitioner, presented September 17-18, 2007, in
Baltimore, MD, by the Johns Hopkins University School of Medicine, Department of Medicine, at Johns Hopkins
Bayview Medical Center. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in
the production of this program.
| IMMUNIZATIONS UPDATE —Lisa G. Winston, MD, Assistant Clinical Professor, Department of Medicine, Division
of Infectious Diseases, University of California, San Francisco, School of Medicine; and Interim Vice Chief of
Medical Service, and Hospital Epidemiologist, San Francisco General Hospital
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| Preventive vaccines: must be extremely safe, especially as disease prevalence wanes or uncommon diseases targeted;
some newer vaccines very expensive
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| Adenovirus: can cause severe disease, even death, among recruits in boot camps and others living in close quarters;
sole manufacturer of vaccine suspended its production, leading to disease resurgence and at least one death
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| Mumps: usually <350 cases/yr in United States, due to widespread use of vaccine (measles-mumps-rubella
[MMR]); ≈6500 cases in 2006, mostly in young adults in 8 contiguous states; strongly associated with college
campuses; most patients had received 2 doses of MMR; ≈90% as effective as measles vaccine; demonstrates that
herd immunity requires widespread administration of highly effective vaccine; however, complication rate lower
than historical levels (no deaths, few hospitalizations); outbreak small, compared to prevaccine era
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| New recommendations for health care workers: if born before 1957—consider one dose of vaccine unless immune
(history of physician-diagnosed mumps, positive serology, or documented evidence of 2 vaccine doses [naturally
occurring mumps produces life-long positive serology, unlike vaccination]); if born during or after 1957—2
doses of vaccine, unless individual has positive serology or history of physician-diagnosed mumps
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| Measles: no endemic transmission in United States, but does occur in other countries; small outbreaks reported in
United States due to imported cases; vaccine highly effective; most cases occurred in young unvaccinated people;
remind parents that measles may be fatal or cause serious, sometimes delayed complications
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Newer Vaccines
| Meningococcal vaccine: traditional vaccine tetravalent polysaccharide vaccine (Menomune); does not cover serogroup
B; poor response among children <2 yr of age (highest-risk population); short duration of protection; boosters
not always effective; does not always elicit T-cell response; does not affect carriage, so does not decrease
prevalence of meningococcal groups in community; new meningococcal vaccine (Menactra)—approved for people
aged 2 to 55 yr; protein conjugate with more robust, longer-lasting effect than older vaccine; still does not cover
serogroup B; does produce good booster response, although no recommendation yet for booster doses; targeted to
adolescents because ≥75% of cases in patients aged >11 yr caused by serogroups covered by vaccine; in younger
patients, >50% of cases caused by serogroup B; routine administration recommended at age 11 to 12 yr (up to 18 yr
of age if living in dormitory); also recommended for military recruits, some travelers, people with terminal complement
deficiency (at increased risk for Neisseria infection) or asplenia; true clinical efficacy still unknown (vaccine
approval based on serologic response); costs >$50,000 per quality-adjusted life year; possible association with
Guillain-Barré syndrome being investigated
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| Pertussis vaccine: childhood—diphtheria toxoid, tetanus toxoid, and acellular pertussis (DTaP); adults and
adolescents—tetanus toxoid and reduced-dose diphtheria toxoid (Td); recommended every 10 yr, or with
wound management; newest vaccine includes full dose of tetanus toxoid, reduced dose of diphtheria toxoid, and
reduced dose of acellular pertussis antigens (Tdap [Boostrix]); vaccination of adolescents and adults recommended
due to large reservoir in this age group and waning immunity with age; ≈600,000 cases occur annually
among people aged 19 to 64 yr; not approved for people >65 yr of age (older tetanus vaccine preferred for that
age group)
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| Who should get Tdap: people aged 19 to 64 yr if >10 yr since last Td vaccination; health care workers; can be given
at 2-yr interval from last Td if necessary; all adults <65 yr who come into contact with infants <1 yr of age;
women in postpartum period; during wound management, can substitute Tdap for one Td dose; children 11 to 12
yr of age should receive Tdap plus meningococcal vaccine; efficacy—vaccine 92% effective, compared to placebo
in ≥1 large study; however, immunity probably wanes over time
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| Influenza vaccines: inactivated, injectable vaccine—only absolute contraindication anaphylactic allergy to eggs;
live attenuated intranasal vaccine (FluMist)—must be resynthesized annually from same viral strains as inactivated
vaccine; heat sensitivity prevents virus from replicating in lower airways; however, cold-adapted (replicates
at colder temperatures found in nose); approved for healthy persons aged 2 to 49 yr; not good choice for
people with chronic diseases
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| Indications for inactivated vaccine: adults >50 yr of age; children between 6 mo and 5 yr of age; anyone >6 mo of
age with chronic medical condition; residents or employees in long-term care facilities; women pregnant during
influenza season; health care workers; anyone who comes into contact with high-risk people; ≈73% of population
targeted for vaccination yearly, but <50% of target group actually vaccinated
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| Side effects and efficacy: injectable vaccine—sore arm; live attenuated vaccine—runny or stuffy nose; in children,
85% to 90% effecacy in preventing influenza A, compared to placebo, and more effective than injectable
vaccine (vaccination of all schoolchildren now being considered); in adults, current evidence suggests live vaccine
somewhat less effective than inactivated
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| Contraindications to live vaccine: outside recommended age groups; presence of chronic medical condition; pregnancy;
history of Guillain-Barré syndrome (relative contraindication for both vaccines); anaphylaxis to eggs;
contact with highly immunosuppressed patients (eg, after organ or bone marrow transplantation)
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| H5N1 vaccine: developed for avian influenza; however, virus has 2 distinct variants (clades); still uncertain if vaccine
will confer cross-clade immunity; approved by Food and Drug Administration (FDA) in April 2007 for inclusion
in national stockpile but not general clinical use; inactivated adjuvant whole virion H5N1 vaccine—
78% of subjects in 2006 study met seropositivity threshold after 2 low doses (10 µg); included in China’s stockpile;
recombinant H5N1 vaccine—confers cross-clade immunity (could overcome problem of viral mutation);
could be first step toward “universal” vaccine that does not require annual administration
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| Varicella vaccine (Varivax): immunizes against chickenpox; recommended for all adults without history of immunity
who are not pregnant or immunocompromised; 2 doses recommended; >95% of adults in United States
have evidence of previous varicella infection
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| Varicella zoster vaccine (Zostavax): same virus as Varivax, but 14 times more potent; in study of >38,000 people, incidence
of zoster infection reduced by 50%; incidence of postherpetic neuralgia reduced by 65%; as age of study
participants increased, efficacy of vaccine for preventing zoster decreased, but efficacy for preventing postherpetic
neuralgia remained same; vaccine now recommended for people >60 yr of age, even with previous history of
zoster; contraindicated for some immunocompromised patients; price $150; cost-effectiveness questionable; must
be stored frozen and used ≤30 min after reconstitution
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| Human papillomavirus (HPV) vaccine: genital HPV most common sexually transmitted infection in United
States; quadrivalent vaccine (Gardasil) licensed by FDA in June 2006; contains major capsid protein (L1) from
HPV types 6, 11, 16, and 18; types 16 and 18 associated with 70% of cervical cancer, while types 6 and 11 associated
with 90% of genital warts; vaccine nearly 100% effective at preventing infection with covered HPV types, as
long as patient not previously infected (most people show evidence of infection with ≥1 viral type ≤1 yr after beginning
sexual activity); for maximal efficacy, recommended for girls aged 11 to 12 yr, with catch-up vaccination
recommended at 13 to 26 yr; given in series of 3 doses over 6 mo; some evidence of partial cross-protection (20%-
30% effectiveness) against nonvaccine serotypes
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| Controversies: whether vaccine should be mandatory for school attendance; expense ($360 for entire series; covered
by some insurers; especially of concern in developing world, where rates of cervical cancer higher than in
United States); impact (if any) on precancerous lesions, cervical cancer (nonvaccine serotypes may replace those
covered in vaccine; no recommendation yet to modify screening practices for cervical cancer or testing for
HPV); use in boys and men
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| ATYPICAL RESPIRATORY INFECTIONS —Jonathan M. Zenilman, MD, Professor of Medicine and Chief, Division
of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD
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| Case 1: 46-yr-old man presents with 5 days of fever, increasing respiratory distress, 2 days of diarrhea, classic community-acquired
pneumonia (CAP), and bilateral interstitial infiltrates; white blood cell count 9,000 cells/µL,
with no shift; mild hyponatremia; patient works as chicken farmer; also had pigeon sick with diarrhea
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| Psittacosis: disease of poultry caused by Chlamydia psittaci bacterium (also seen in pigeons); rule out viral or influenza
pneumonia; check for HIV risk factors (rule out Pneumocystis jirovecii pneumonia [PCP]); bilateral
interstitial infiltrates point away from legionellosis, which is usually lobar, but rule it out to be safe
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| Management issues: determine if patient should be admitted to hospital; determine Pneumonia Patient Outcomes
Research Team (PORT) score; however, no fast point-of-care tests available; watch patient for 4 to 6 hr; treat
psittacosis with doxycycline
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| Case 2: 38-yr-old man institutionalized long term with cerebral palsy admitted to intensive care unit (ICU) with
CAP and interstitial infiltrates; currently on day 8 of antibiotics (third-generation cephalosporin and macrolide);
need for oxygen increasing
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| Differential diagnosis: Klebsiella pneumonia (usually lobar, not interstitial, and generally covered by third-generation
cephalosporin); actual diagnosis PCP; patient had been sexually abused while institutionalized
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| Case 3: man with 5-yr history of cough; fever and chills several months before presenting for treatment; otherwise
healthy; chest x-ray shows 6 x 5-cm perihilar node; after fiberoptic bronchoscopy, pulmonologist diagnosed
probable cancer
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| Differential diagnosis: sarcoidosis, tuberculosis (purified protein derivative [PPD] and biopsy negative); actual diagnosis
histoplasmosis; patient had benign lymph node with multiple granulomas and lymphadenitis with foci of
necrosis, as well as Grocott-Gomori methenamine-silver nitrate (GMS) stain suggestive of histoplasma; urine
negative for histoplasma antigen, but patient had histoplasma fibrosing mediastinitis, which is usually antigen-
negative; with treatment, area becomes fibrotic within 2 to 3 yr; key point—diagnosis required tissue biopsy
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| Case 4: 29-yr-old man hospitalized for 1 wk with diagnosis of Pseudomonas pneumonia; no risk factors; HIV-negative;
sputum cultures also grew Mycobacterium reported as nontuberculous but not fully speciated; postdischarge
chest x-ray showed lingular infiltrate; unhappy with progress, patient made appointment at infectious disease
clinic 4 mo after hospitalization; had grand mal seizure in clinic; admitted to hospital, treated with levofloxacin
and azithromycin; seizure work-up negative; forced expiratory volume in 1 second (FEV1 ) 55% of predicted; patient
had Mycobacterium abscessus infection; sweat test positive for cystic fibrosis
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| Cystic fibrosis: complex series of genetic mutations; should be part of differential diagnosis when patients present
with unusual organisms
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| Diagnostic pearls: history 80% to 90% of story; male patients with cystic fibrosis often sterile; work-up should include
occupational and family history; if patient has recurrent infections such as methicillin-resistant Staphylococcus
aureus (MRSA) cellulitis, consider underlying immunodeficiency or atopic dermatitis; also consider
behavioral risk factors, current comorbidities, pace of symptom occurrence, and patient’s age
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| Nontuberculous mycobacterial disease: incidence increasing (reasons unclear); patient may see 6 to 10 physicians
before receiving accurate diagnosis
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| Sample case: woman presents with chronic cough for 2 to 3 yr; previous chest x-ray normal; diagnosed with CAP,
sent home with antibiotics; now noticing blood in phlegm; never smoked; had frequent bronchitis in childhood and
asthma in adolescence; now has chronic postnasal drip; chest x-ray shows hazy opacity on border on posteroanterior
view, with irregular densities over heart in retrosternal region; such patients usually have abnormalities in middle
lobe, or lingular infiltrates with interstitial patterns; however, as disease progresses, bronchiectasis develops
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| Pearls: mycobacteria live in local soil and water; differentiate between community-acquired pulmonary disease and
disease related to host immunosuppression; mycobacteria also cause postsurgical infections (eg, postcardiac mediastinitis
from atypical mycobacterial infection with rapidly growing species); “fish tank fingers” caused by
Mycobacterium marinum, which lives in brackish water; people with chronic obstructive pulmonary disease also
at high risk for infection; unifying factor chronic infiltrates with progressive decrease in pulmonary function;
suspect atypical mycobacterial pulmonary infection in these patients; ask laboratory to test sputum for acid-fast
bacilli
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| Classic patient: middle-aged or older white woman; usually healthy otherwise; slender build; usually has initially
dry cough of insidious onset; secretions vary; often reports fever, chills, night sweats, vague malaise, or diminished
energy; tuberculosis work-up negative; occasional focal chest discomfort; chest x-rays typically show
shadows over lower or middle lobe; refer to pulmonologist or infectious disease expert for more work-up; differential
diagnosis—includes cystic fibrosis, ciliary dyskinesia, α-1 antitrypsin disease in someone with neurologic
dysfunction, previous histoplasmosis, or tuberculosis (may be risk factor)
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| Treatment: identify organism; determine susceptibility to antibiotics; treat for 12 to 24 mo
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Suggested Reading
Centers for Disease Control and Prevention (CDC): Update: Measles—United States, January-July, 2008. Morbidity
and Mortality Weekly Report 57:893, 2008; Cunha BA: The atypical pneumonias: clinical diagnosis and importance.
Clin Microbiol Infect 12 Suppl 3:12, 2006; Davidkin I et al: Persistence of measles, mumps, and rubella antibodies in an
MMR-vaccinated cohort: a 20-year follow-up. J Infect Dis 197:950, 2008; Fedson DS: New technologies for meeting the global
demand for pandemic influenza vaccines. Biologicals August 18, 2008 [Epub ahead of print]; Fiore AE et al: Prevention
and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm
Rep 57(RR-7):1, 2008; Jarzembowski JA, Young MB: Nontuberculous mycobacterial infections. Arch Pathol
Lab Med 132:1333, 2008; Kim JJ, Goldie SJ: Health and economic implications of HPV vaccination in the United States. N
Engl J Med 359:821, 2008; Knuf M et al: A combination vaccine against measles, mumps, rubella and varicella. Drugs Today
(Barc) 44:279, 2008; Marin M et al: Mumps vaccination coverage and vaccine effectiveness in a large outbreak among
college students—Iowa, 2006. Vaccine 26:3601, 2008; Pandeli V, Ernest D: A case of fulminant psittacosis. Crit Care
Resusc 8:40, 2006; Poland GA, Sambhara S: Vaccines against influenza A (H5N1): evidence of progress. J Infect Dis
198:629, 2008; Shinefield HRet al: Varicella immunogenicity with 1- and 2-dose regimens of measles-mumps-rubella-varicella
vaccine. J Infect Dis 197 Suppl 2:S152, 2008.
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